ПОЛІФУНКЦІОНАЛЬНІ ПОХІДНІ ТІАЗОЛУ/ТІАЗОЛІДИНОНУ ЯК НОВІ КЛАСИ ГЕТЕРОЦИКЛІЧНИХ СПОЛУК З НОВИМИ МЕХАНІЗМАМИ РЕАЛІЗАЦІЇ ПРОТИПУХЛИННОЇ АКТИВНОСТІ
Thiazole and thiazolidinone derivatives constitute an important class of heterocyclic compounds, widely investigated in modern medicinal chemistry for their diverse biological activities and significant potential for structural modification. Particular attention has focused on their anticancer prope...
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Experimental Oncology| _version_ | 1868113233185865728 |
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| author | Pasichnyk, S. Lozynskyi, A. Lesyk, R. Matviiv, V. Snizhko, B. |
| author_facet | Pasichnyk, S. Lozynskyi, A. Lesyk, R. Matviiv, V. Snizhko, B. |
| author_institution_txt_mv | [
{
"author": "S. Pasichnyk",
"institution": "Danylo Halytsky Lviv National Medical University, Lviv, Ukraine"
},
{
"author": "A. Lozynskyi",
"institution": "Danylo Halytsky Lviv National Medical University, Lviv, Ukraine"
},
{
"author": "R. Lesyk",
"institution": "Danylo Halytsky Lviv National Medical University, Lviv, Ukraine"
},
{
"author": "V. Matviiv",
"institution": "Danylo Halytsky Lviv National Medical University, Lviv, Ukraine"
},
{
"author": "B. Snizhko",
"institution": "Danylo Halytsky Lviv National Medical University, Lviv, Ukraine"
}
] |
| author_sort | Pasichnyk, S. |
| baseUrl_str | https://exp-oncology.com.ua/index.php/Exp/oai |
| collection | OJS |
| datestamp_date | 2026-06-15T10:40:23Z |
| description | Thiazole and thiazolidinone derivatives constitute an important class of heterocyclic compounds, widely investigated in modern medicinal chemistry for their diverse biological activities and significant potential for structural modification. Particular attention has focused on their anticancer properties and the design of multifunctional hybrid molecules with improved pharmacological profiles. This review summarizes recent advances in the synthesis and biological evaluation of functionally substituted condensed and non-condensed thiazole/thiazolidinone derivatives with anticancer activity. Available literature demonstrates that many of these compounds exhibit pronounced cytotoxic and pro-apoptotic effects across various tumor models. Their biological activity is associated with interactions with multiple molecular targets, including PPARγ receptors, integrins, PI3K/mtOR signaling pathways, histone deacetylases, matrix metalloproteina- ses, StAt3, and Pim-kinases. These multitarget mechanisms highlight the potential of these heterocyclic scaffolds for developing innovative anticancer agents. Analysis of structure–activity relationships has revealed promising directions for further optimization of the lead compounds. Overall, thiazole and thiazolidinone derivatives remain attractive plat- forms for the rational design of new anticancer drugs with improved selectivity and reduced toxicity. |
| doi_str_mv | 10.15407/exp-oncology.2026.01.003 |
| first_indexed | 2026-06-15T01:00:21Z |
| format | Article |
| fulltext |
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 3
Drug design is an extremely lengthy, labor-inten-
sive, and multi-stage process that takes many
years and requires enormous financial invest-
ment. One of the key stages in drug development
that is closely related to modern pharmaceutical
and medical chemistry is the search for and opti-
mization of lead compounds. Identification of
specific compounds is the starting point for ob-
taining molecules with the necessary activity, se-
lectivity, and acceptable ADMET parameters (ab-
sorption, distribution, metabolism, elimination,
and toxicity).
Sources of lead compounds may include the en-
dogenous ligands, in particular enzyme substrates,
transport proteins, or receptor agonists; other li-
gands, including existing drugs, compounds isola
ted during drug metabolism, or substances at clin-
ical trial stages; derivatives identified through
screening of chemical libraries, including naturally
occurring compounds [1].
https://doi.org/10.15407/exp-oncology.2026.01.003
S. Pasichnyk *, A. Lozynskyi, R. Lesyk, V. Matviiv, B. Snizhko
Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
* Correspondence: E-mail: pasichnykdoctua@gmail.com
Polyfunctional Thiazole/Thiazolidinone
Derivatives as a New Class of Heterocyclic
Compounds with Novel Mechanisms
of Anticancer Activity
Thiazole and thiazolidinone derivatives constitute an important class of heterocyclic compounds, widely investigated in
modern medicinal chemistry for their diverse biological activities and significant potential for structural modification.
Particular attention has focused on their anticancer properties and the design of multifunctional hybrid molecules with
improved pharmacological profiles. This review summarizes recent advances in the synthesis and biological evaluation
of functionally substituted condensed and non-condensed thiazole/thiazolidinone derivatives with anticancer activity.
Available literature demonstrates that many of these compounds exhibit pronounced cytotoxic and pro-apoptotic effects
across various tumor models. Their biological activity is associated with interactions with multiple molecular targets,
including PPARγ receptors, integrins, PI3K/mTOR signaling pathways, histone deacetylases, matrix metalloproteina
ses, STAT3, and Pim-kinases. These multitarget mechanisms highlight the potential of these heterocyclic scaffolds for
developing innovative anticancer agents. Analysis of structure–activity relationships has revealed promising directions
for further optimization of the lead compounds. Overall, thiazole and thiazolidinone derivatives remain attractive plat-
forms for the rational design of new anticancer drugs with improved selectivity and reduced toxicity.
Keywords: thiazole, thiazolidinone, antitumor activity, biotargets, hybrid molecules.
Reviews
C i t a t i o n: Pasichnyk S, Lozynskyi A, Lesyk R, Matviiv V, Snizhko B. Polyfunctional thiazole/thiazolidinone derivatives
as a new class of heterocyclic compounds with novel mechanisms of anticancer activity. Exp Oncol. 2026; 48(1): 3-9.
https://doi.org/10.15407/exp-oncology.2026.01.003
© PH “Akademperiodyka” of the NAS of Ukraine, 2026. This is an open access article under the CC BY-NC-ND license
(https://creativecommons.org/licenses/by-nc-nd/4.0/)
4 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
S. Pasichnyk, A. Lozynskyi, R. Lesyk, V. Matviiv, B. Snizhko
The search for lead compounds is based on us-
ing two key elements: high-throughput screening
and synthetic approaches, which include tar-
get-oriented synthesis, synthesis of focused libra
ries, diversity-oriented synthesis (DOS), etc. [2].
In turn, DOS includes the following strategies:
multicomponent reactions, cycloaddition reac-
tions, cyclization and tandem reactions, the con-
cept of combining functional groups, and the stra
tegy of privileged structures [3].
It should be noted that thiazole derivatives and
their functional derivatives are a class of com-
pounds that can serve as the basis for obtaining
lead compounds, as they possess not only a wide
spectrum of biological activity but also significant
potential for further chemical modification. The
thiazole core forms the basis of numerous natu-
rally occurring compounds, including the glyco-
sidic anticancer antibiotic bleomycin; macrolides
latrunculin A, leinamycins, and langbiabelins; cy-
clic peptides argyrin A, gracyptide, promotiocin,
and microcyclamides; linear peptides tubulysins;
and diterpenes eretazoles, which are currently
registered as anticancer drugs or are at preclinical
study stages [4].
Among natural thiazole-based compounds and
their functional derivatives with antimicrobial ac-
tivity, β-lactam antibiotics of the penicillin and
monobactam series, thiopeptide antibiotics (noca-
thiacin, nosiheptide, and thiomuracin A), as well
as cystothiazoles A–F with notable antifungal ac-
tivity have been identified. On the other hand, thi-
azole derivatives form the basis of numerous syn-
thetic drugs, including pramipexole as a dopamine
receptor agonist used for the treatment of Parkin-
son’s disease and Restless Legs Syndrome (RLS);
HIV-1 protease inhibitor ritonavir and CYP3A4
inhibitor cobicistat, used in the treatment of HIV
infection; H2-histamine receptor antagonists niza-
tidine and famotidine as anti-ulcer drugs; antihel-
mintic drugs thiabendazole, levamisole, and tet
ramisole; riluzole as a therapy for amyotrophic la
teral sclerosis; antidiabetic drugs pioglitazone,
troglitazone, rosiglitazone, lobeglitazone as PPARγ
receptor agonists; non-purine xanthine oxidase in-
hibitor febuxostat as an antigout agent; non-steroi-
dal anti-inflammatory drug meloxicam; tyrosine
kinase inhibitor dasatinib as an anticancer agent;
coenzyme vitamin B1 cocarboxylase; sulfonamide
drugs sulfathiazole and phthalylsulfothiazole; and
radiopharmaceutical for Alzheimer’s disease diag-
nosis flutemetamol (18F) [5].
Among the functional thiazole derivatives, there
is also a large number of synthetic compounds at
preclinical research stages, including clomethiazole
as an allosteric modulator of type A GABA recep-
tors for the treatment of alcohol withdrawal syn-
drome; niridazole as an antischistosomal agent; the
aldose reductase inhibitor zopolrestat, used in the
treatment of diabetic complications; teneligliptin,
balaglitazone, mitoglitazone, 2,4-thiazolidinedione,
and galicin as agents for the treatment of type 2 di-
abetes; letosteine as a mucolytic agent in the treat-
ment of bronchopneumopathies; the hypolipide
mic agent netoglitazone; pidotimod as an immu-
nomodulatory agent; the A2 adenosine receptor
agonist tozadenant as an agent for the treatment of
cocaine addiction; efatutazone, quizartinib, pid-
narulex, and epalrestat as anticancer agents; talaro-
zole as an agent for the treatment of psoriasis and
other skin diseases; piprozoline in the therapy of
biliary tract pathology and dyspepsia; the hypouri-
cemic agent dotinurad; ebopiprant as an agent used
in preterm labor; and the JNK kinase inhibitor ben-
tamipod for the treatment of endometriosis [6].
Each of the above-mentioned drugs or potential
“lead-like compounds” has been designed using
completely different approaches; however, what
they all have in common is a process that involves
chemical modification of thiazole derivatives, fol-
lowed by obtaining molecules possessing certain
biological activity and serving as the basis for the
construction of lead compounds [7].
Considering the arguments presented, the search
for new biologically active compounds with anti-
cancer activity among multifunctional derivatives
based on thiazole/thiazolidinone is a justified and
promising direction in modern medical and phar-
maceutical chemistry.
A critical review of the literature on the synthesis
of thiazole and thiazolidinone derivatives, their
structural analogs, and the evaluation of anticancer
activity was carried out. Special attention was paid
to identifying molecular biotargets, such as PPARγ
receptors, integrins, PI3K/mTOR enzymes, HDAC,
MMP, STAT3, Pim-kinases, and other signaling
targets that determine the mechanisms of cytoto
xic, pro-apoptotic, and anticancer action. We at-
tempted to systematize modern approaches to as-
sessing the anticancer potential of many functio
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 5
Polyfunctional Thiazole/Thiazolidinone Derivatives as a New Class of Heterocyclic Compounds
nally substituted condensed and non-condensed
derivatives based on thiazole/4-thiazolidinone, in-
cluding hybrid molecules containing the fragments
of natural compounds in their structure.
While the literature extensively covers the syn-
thesis and anticancer screening of 4-thiazolidinone
derivatives, few studies investigate their specific
biological mechanisms. Modern medicinal che
mistry aims to identify lead compounds for drug
development; therefore, simply finding highly ac-
tive agents is not enough. These compounds must
undergo rigorous preclinical and clinical trials, as
well as toxicity assessments. Only after these exten-
sive studies can we determine if a compound is tru-
ly viable for medical practice. Accordingly, this re-
view is devoted to the analysis of the literature on
the mechanisms of biological activity of 4-thiazo-
lidinone derivatives exemplified by the existing
drugs or compounds at the preclinical trial stage or
other in-depth studies.
Among the 4-thiazolidinone-based derivatives,
the most well-known drugs are glitazones, a group
of antidiabetic agents with a well-established
mechanism of biological activity. The cellular
mechanism of the action of glitazones is mediated
by binding to and activating the peroxisome pro-
liferator-activated receptor gamma (PPARγ),
a nuclear receptor that acts as a transcription fac-
tor, regulating the transcription and expression of
specific genes [8—10]. Together with other iso-
forms, such as PPARα and PPARβ, it belongs to
the same group as thyroid hormone and steroid
receptors. The expression level of PPARγ is the
highest in adipocytes, intestinal cells, and macro-
phages, but very low in most other tissues, inclu
ding muscle tissue. Endogenous ligands for PPARγ
are long-chain unsaturated fatty acids and prosta-
noids. Upon activation, PPARγ heterodimerizes
with the retinoid X receptor, and the activated
complex subsequently binds to specific DNA seg-
ments to induce transcription of PPAR-responsive
elements [11].
In addition to metabolic effects, PPARγ plays an
important role in the regulation of cell prolifera-
tion, differentiation, and apoptosis, which deter-
mines its involvement in carcinogenesis. The dys-
regulation of PPARγ expression or activity is asso-
ciated with the development and progression of
several types of malignant tumors, including co
lorectal, breast, prostate, and lung cancers. The ac-
tivation of PPARγ in some models can suppress tu-
mor cell proliferation and induce apoptosis; ho
wever, under other conditions, overexpression of
this receptor promotes lipid accumulation, remo
deling of the tumor microenvironment, and the for-
mation of a pro-tumorigenic phenotype. In particu-
lar, PPARγ receptors affect malignant tumor growth
by suppressing cancer cell proliferation, promoting
apoptosis, and inducing intercellular adhesion and
inflammation in the tumor microenvironment [12].
This dual role of PPARγ makes it a promising yet
complex target for the development of new antican-
cer agents among 4-thiazolidinone derivatives.
It should be noted that not only glitazones but
also other 4-thiazolidinone derivatives have af-
finity for PPARγ receptors. For example, in stud-
ies by Szychowski et al. [13], functionalized thi-
azolidinone derivatives were shown to exhibit
anticancer activity against the human squamous
cell carcinoma line SCC-15 with the involvement
of PPARγ receptors.
One of the well-studied biological activities of thi-
azolidinone derivatives and their structural analogs
is their anti-inflammatory effect [14]. The most ex-
tensively studied representative is darbofelon, a dual
inhibitor of prostaglandin PGF2R and leukotriene
LTB4 synthesis. Darbofelon selectively inhibits cy-
clooxygenase-2 (COX-2) (IC50 0.19 μM) while
COX-1 is inhibited significantly less (IC50 20 μM).
Preclinical studies have shown no ulcerogenic ef-
fect upon its oral administration [15], and the
drug is currently in Phase III clinical trials for the
treatment of rheumatoid arthritis. Darbofelon’s
selectivity for COX isoforms significantly exceeds
that of meloxicam (COX-1: IC50 36.6 μM; COX-2:
IC50 4.7 μM) [15].
Importantly, in addition to its pronounced an-
ti-inflammatory activity, darbofelon is character-
ized by notable anticancer activity. Ye et al. [16]
demonstrated its dose-dependent suppression of
cell viability in the human non-small cell lung car-
cinoma line NCI-H460, disruption of the cell cy-
cle, and induction of apoptosis through the acti-
vation of caspases-3 and -8; a similar effect was
observed for its structural analog (PD0167570).
Among the thiazolidinone derivatives and struc-
tural analogs, a large number of compounds with
significant anticancer effects have also been identi-
fied [17]. Most studies on thiazolidinone and thi-
azole derivatives focus on in vitro cytotoxicity rather
6 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
S. Pasichnyk, A. Lozynskyi, R. Lesyk, V. Matviiv, B. Snizhko
than specific anticancer mechanisms. Identifying
biological targets remains difficult because tumor
development involves complex, poorly understood
enzymatic networks. Despite these challenges, re-
searchers have successfully identified probable bio
targets for several derivatives in this class. In parti
cular, some thiazolidinone derivatives and structur-
al analogs have been shown to possess antidiabetic
and anti-inflammatory activity combined with an-
ticancer activity. In addition, the quinoxaline-thi-
azolidinone derivative was identified as a highly ac-
tive inhibitor of gamma phosphoinositide 3-kinase
(PI3K), an enzyme that plays a key role in regulat-
ing tumor growth [18]. This compound selectively
inhibits the enzymatic activity of PI3K gamma, as
well as its mediated signaling system and chemo-
taxis in vitro and in vivo. The compound also
showed moderate activity against other PI3K iso-
forms. The structurally related pyridinylquino-
line-thiazolidinone derivative was identified as a
dual PI3K/mTOR inhibitor. This compound is cur-
rently in Phase I clinical trials in patients with sol-
id tumors or lymphomas [19]. Moreover, recently
published clinical study results have demonstrated
that the derivative exhibits cytotoxic activity against
head and neck squamous cell carcinoma in mouse
xenograft models [20].
A large number of biologically active compounds
target necroptosis, an alternative form of pro-
grammed cell death, contributing to oncogenesis
and metastasis [21]. Zheng et al. [22] identified
highly active necroptosis inhibitors among thiazo-
lidinone-thiazole-pyrazole hybrid molecules.
Dayam et al. [23] identified a highly active in-
hibitor of the integrin αVβ3 among the 2-aryli
mino-5-ylidene-4-thiazolidinone derivatives
(IC50 0.03 μM). Integrin αVβ3 is considered a po-
tential target for biologically active compounds,
as its abnormal expression is associated with va
rious pathological conditions, including cancer
angiogenesis [24].
Among derivatives based on 2-thioxo-4-thiazo-
lidinone (rhodanine), several highly active com-
pounds with anticancer activity have also been
identified, and for some of them, the mechanisms
of biological activity have been thoroughly estab-
lished. In particular, the 5-ylidene-3-phenyl-
rhodanine derivative containing a cinnamaldehyde
fragment in its structure is capable of stabilizing the
binding of integrin αMβ2 with its endogenous li-
gands proMMP-9 and fibrinogen. The compound
inhibits αMβ2-dependent in vitro cell migration
and inflammation-induced neutrophil migration
in vivo [25]. Also, derivative 1.153 suppressed the
growth of leukemia and lymphoma xenografts in
mice and significantly prolonged their survival.
Further studies on the activity of the compound
against various types of leukemia, particularly lym-
phomas, are ongoing [26].
The rhodanine-benzimidazole derivative was
identified as a selective inhibitor of Pim-1, -2, and
-3 kinases with IC50 values of 16, 13, and 6.4 nM,
respectively. Moreover, the compound inhibited the
proliferation of solid tumor and hematologic can-
cer cell lines at submicromolar concentrations. In
the studied cell lines, the compound inhibited
phosphorylation of Pim signaling substrates, dis-
rupted the cell cycle, and induced apoptosis [27].
Vatolin et al. [28] identified the 5-ylidene-
3-phenylrhodanine derivative as an inhibitor of
protein disulfide isomerase (PDI). It was estab-
lished that multiple myeloma cells produce much
more disulfide-containing proteins compared to
other cells. Inhibition of PDI, which is key for
protein folding in the endoplasmic reticulum
(ER), induces ER stress, subsequently leading to
the death of this tumor cell type [29]. The com-
pound was shown to bind PDI A1, A3, and A4
in multiple myeloma cells and demonstrated ap-
proximately 100-fold stronger inhibition of this
enzyme compared to the known inhibitors
PACMA 31 and LOC14 [27].
Huang et al. [30] identified the rhodanine deri
vative as a c-Myc inhibitor. c-Myc heterodimerizes
with the Max-interacting protein, resulting in trans-
activation of downstream target genes in leukemo-
genesis [31]. The rhodanine-carboxylic acid deriva-
tive was identified as an inhibitor of the interaction
between the BH3 domain and Bcl-xL [32], which is
important for the induction of apoptosis [33].
Among rhodanine-based derivatives, the com-
pound was also identified as a highly active inhib-
itor of JNK-stimulating phosphatase-1 (JSP-1) [34].
JSP-1 phosphatase belongs to the class of atypical
dual-specificity phosphatases, which regulate var-
ious cellular processes, including growth, prolifer-
ation, differentiation, metabolism, immune re-
sponse, cell–cell adhesion, and cell–matrix con-
tacts. In the search for potential anticancer agents,
JSP-1 phosphatase is an interesting target, particu-
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 7
Polyfunctional Thiazole/Thiazolidinone Derivatives as a New Class of Heterocyclic Compounds
larly for cancer types associated with the dysfunc-
tion of the Jnk1 signaling system [35].
Carter et al. [36] reported the rhodanine deriva-
tive as a highly active inhibitor of tumor necrosis
factor alpha (TNF-α). TNF-α, a pleiotropic cytokine,
plays a central role in inflammation and immune
system homeostasis and is involved in a range of
pathological states, including chronic inflammation,
autoimmune diseases, and cancer [37, 38].
Among the thiazole derivatives, several highly
active anticancer agents with established mecha-
nisms of action have also been identified. Anh et
al. [39] identified 2-(4-chlorobenzamido)-N-hyd
roxythiazole-4-carboxamide as a highly effective
histone deacetylase (HDAC) inhibitor. The IC50 of
the compound was 0.033 μM, comparable to that
of a typical inhibitor of this enzyme, N-hy-
droxy-N’-phenyl-octanediamide (vorinostat) (IC50
0.025 μM). It is known that the overexpression of
various classes of HDACs increases cell prolifera-
tion and blocks apoptosis while simultaneously
preventing cell differentiation, and contributes to
angiogenesis and cell migration [40].
Ge et al. [41] synthesized a series of thiazole de-
rivatives, among which one compound exhibited
the highest inhibitory activity against matrix metal-
loproteinases (MMP) 2 and 8. These enzymes play
a role in the extracellular matrix remodeling, pro-
teolytic degradation of the extracellular matrix, dis-
ruption of cell–cell and cell–matrix interactions,
cancer cell migration, and angiogenesis [42].
In the work by Hu et al. [43], thiazole derivatives
were reported to disrupt the Hec1/Nek2 interac-
tion — critical mitotic regulators that ensure prop-
er chromosome segregation, whose overexpression
is often observed in cancers with poor prognosis.
Wilson et al. [44] synthesized a series of thio-
phene-2-carboxamides containing a 2-aminothi-
azole fragment and studied their ability to bind
urokinase, a key enzyme involved in metastasis.
The authors identified several compounds from
this class that exhibited inhibitory activity against
this enzyme in the submicromolar range.
In several studies, certain condensed thiazole de-
rivatives were also shown to exhibit significant anti-
cancer activity, and their molecular targets were
identified. Shen et al. [45] synthesized a triterpenoid
orodonin derivative containing a thiazole fragment
that demonstrated strong inhibitory activity against
signal transducer and activator of transcription 3
(STAT3). Ali et al. [46] synthesized para-cyclophe-
nyl-thiazole-naphthoquinone derivatives with high
anticancer activity against SK-MEL-5 melanoma
cells, and potent inhibitory activity against certain
cyclin-dependent kinase isoforms.
Xie et al. [47] synthesized a benzothiazole de-
rivative with antiproliferative activity against
HCT‑116 colon carcinoma, MCF-7 breast adeno-
carcinoma, U87 MG glioma, and A549 epithelial
lung carcinoma cell lines, and potent inhibitory
activity toward the PI3K/mTOR signaling path-
way. Luke et al. [48] reported the synthesis of thi-
azolopyrimidine derivatives containing a pyrazole
fragment, identifying a highly active compound
that exhibited strong inhibitory activity against
the tyrosine kinase receptor Tie2.
It is noteworthy that Tie2 overexpression is ob-
served in tumor vasculature. Also, Tie2 is expressed
outside the vascular system in various cancers, in-
cluding leukemia, gastric cancer, breast cancer, and
glioma [49]. Among thiazolo[3,2-a] pyrimidine de-
rivatives, a highly active compound was identified,
showing strong DNA-binding properties that ex-
ceeded those of doxorubicin used as a control, as
reported by Al-Rashood et al. [50].
In conclusion, many thiazole/thiazolidinone de-
rivatives have been shown to exert anticancer ac-
tivity both in vitro and in vivo via the inhibition of
the key molecules involved in regulating apoptosis,
necroptosis, cell adhesion, and metastasis. Many of
these derivatives can interact with specific mole
cular targets, which makes them promising candi-
dates for further optimization and the development
of new anticancer therapeutics.
Considering the above, thiazole/thiazolidinone
derivatives and their structural analogs possess sig-
nificant synthetic and pharmacological potential
for research aimed at identifying potential “lead-
like” molecules as a basis for the development of
novel anticancer drugs.
Acknowledgments
This work was supported by the National Research
Foundation of Ukraine (2023.05/0021 and
2025.02/0014); the research and development pro
ject 0125U003375; a grant from the Ministry of
Education and Science of Ukraine (0125U001794);
grants from the Ministry of Health of Ukraine
(0126U001827 and 0126U001771).
8 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
S. Pasichnyk, A. Lozynskyi, R. Lesyk, V. Matviiv, B. Snizhko
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Submitted: April 1, 2026
10 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
S. Pasichnyk, A. Lozynskyi, R. Lesyk, V. Matviiv, B. Snizhko
С. Пасічник, А. Лозинський,
Р. Лесик, В. Матвіїв, Б. Сніжко
ДНТ «Львівський національний медичний університет
імені Данила Галицького», Львів, Україна
ПОЛІФУНКЦІОНАЛЬНІ ПОХІДНІ ТІАЗОЛУ/ТІАЗОЛІДИНОНУ
ЯК НОВІ КЛАСИ ГЕТЕРОЦИКЛІЧНИХ СПОЛУК З НОВИМИ
МЕХАНІЗМАМИ РЕАЛІЗАЦІЇ ПРОТИПУХЛИННОЇ АКТИВНОСТІ
Похідні тіазолу та тіазолідинону є важливим класом гетероциклічних сполук, які активно досліджуються в сучас-
ній медичній та фармацевтичній хімії завдяки широкому спектру біологічної активності та значному потенціалу
для структурної модифікації. Особливий інтерес викликають їхні протипухлинні властивості та можливість ство-
рення поліфункціональних гібридних молекул з покращеними фармакологічними характеристиками. У даному
огляді узагальнено сучасні дані щодо синтезу та біологічного дослідження функціонально заміщених конденсова-
них і неконденсованих похідних тіазолу та тіазолідинону з протипухлинною активністю. Проаналізовано літера-
турні джерела, що демонструють виражену цитотоксичну та проапоптотичну активність багатьох представників
цього класу сполук у різних пухлинних моделях. Показано, що їх біологічна дія пов’язана з взаємодією з низкою
молекулярних мішеней, зокрема рецепторами PPARγ, інтегринами, сигнальними шляхами PI3K/mTOR, гістон-
дезацетилазами, матриксними металопротеїназами, STAT3 та Pim-кіназами. Такий мультитаргетний механізм
дії підкреслює значний потенціал цих гетероциклічних систем у створенні нових протипухлинних препаратів.
Аналіз залежностей «структура–активність» дозволяє визначити перспективні напрямки подальшої оптимізації
цих сполук як базових структур. Отже, похідні тіазолу та тіазолідинону залишаються привабливою платформою
для раціонального дизайну нових протиракових агентів з підвищеною селективністю та зниженою токсичністю.
Ключові слова: тіазол, тіазолідинон, протипухлинна активність, біологічні мішені, гібридні молекули.
|
| id | oai:ojs2.ex.aqua-time.com.ua:article-612 |
| institution | Experimental Oncology |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-06-16T01:00:10Z |
| publishDate | 2026 |
| publisher | PH Akademperiodyka |
| record_format | ojs |
| resource_txt_mv | exp-oncologycomua/0d/5e4f4dc167291a5057cf15762078510d.pdf |
| spelling | oai:ojs2.ex.aqua-time.com.ua:article-6122026-06-15T10:40:23Z Polyfunctional Thiazole/Thiazolidinone Derivatives as a New Class of Heterocyclic Compounds with Novel Mechanisms of Anticancer Activity ПОЛІФУНКЦІОНАЛЬНІ ПОХІДНІ ТІАЗОЛУ/ТІАЗОЛІДИНОНУ ЯК НОВІ КЛАСИ ГЕТЕРОЦИКЛІЧНИХ СПОЛУК З НОВИМИ МЕХАНІЗМАМИ РЕАЛІЗАЦІЇ ПРОТИПУХЛИННОЇ АКТИВНОСТІ Pasichnyk, S. Lozynskyi, A. Lesyk, R. Matviiv, V. Snizhko, B. тіазол, тіазолідинон, протипухлинна активність, біологічні мішені, гібридні молекули thiazole, thiazolidinone, antitumor activity, biotargets, hybrid molecules Thiazole and thiazolidinone derivatives constitute an important class of heterocyclic compounds, widely investigated in modern medicinal chemistry for their diverse biological activities and significant potential for structural modification. Particular attention has focused on their anticancer properties and the design of multifunctional hybrid molecules with improved pharmacological profiles. This review summarizes recent advances in the synthesis and biological evaluation of functionally substituted condensed and non-condensed thiazole/thiazolidinone derivatives with anticancer activity. Available literature demonstrates that many of these compounds exhibit pronounced cytotoxic and pro-apoptotic effects across various tumor models. Their biological activity is associated with interactions with multiple molecular targets, including PPARγ receptors, integrins, PI3K/mtOR signaling pathways, histone deacetylases, matrix metalloproteina- ses, StAt3, and Pim-kinases. These multitarget mechanisms highlight the potential of these heterocyclic scaffolds for developing innovative anticancer agents. Analysis of structure–activity relationships has revealed promising directions for further optimization of the lead compounds. Overall, thiazole and thiazolidinone derivatives remain attractive plat- forms for the rational design of new anticancer drugs with improved selectivity and reduced toxicity. Похідні тіазолу та тіазолідинону є важливим класом гетероциклічних сполук, які активно досліджуються в сучас- ній медичній та фармацевтичній хімії завдяки широкому спектру біологічної активності та значному потенціалу для структурної модифікації. Особливий інтерес викликають їхні протипухлинні властивості та можливість ство- рення поліфункціональних гібридних молекул з покращеними фармакологічними характеристиками. У даному огляді узагальнено сучасні дані щодо синтезу та біологічного дослідження функціонально заміщених конденсова- них і неконденсованих похідних тіазолу та тіазолідинону з протипухлинною активністю. Проаналізовано літера- турні джерела, що демонструють виражену цитотоксичну та проапоптотичну активність багатьох представників цього класу сполук у різних пухлинних моделях. Показано, що їх біологічна дія пов’язана з взаємодією з низкою молекулярних мішеней, зокрема рецепторами PPARγ, інтегринами, сигнальними шляхами PI3K/mtOR, гістон- дезацетилазами, матриксними металопротеїназами, StAt3 та Pim-кіназами. Такий мультитаргетний механізм дії підкреслює значний потенціал цих гетероциклічних систем у створенні нових протипухлинних препаратів. Аналіз залежностей «структура–активність» дозволяє визначити перспективні напрямки подальшої оптимізації цих сполук як базових структур. Отже, похідні тіазолу та тіазолідинону залишаються привабливою платформою для раціонального дизайну нових протиракових агентів з підвищеною селективністю та зниженою токсичністю. PH Akademperiodyka 2026-06-14 Article Article application/pdf https://exp-oncology.com.ua/index.php/Exp/article/view/612 10.15407/exp-oncology.2026.01.003 Experimental Oncology; Vol. 48 No. 1 (2026): Experimental Oncology; 3-10 Експериментальна онкологія; Том 48 № 1 (2026): Експериментальна онкологія; 3-10 2312-8852 1812-9269 10.15407/exp-oncology.2026.01 en https://exp-oncology.com.ua/index.php/Exp/article/view/612/457 Copyright (c) 2026 Experimental Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| spellingShingle | тіазол тіазолідинон протипухлинна активність біологічні мішені гібридні молекули Pasichnyk, S. Lozynskyi, A. Lesyk, R. Matviiv, V. Snizhko, B. ПОЛІФУНКЦІОНАЛЬНІ ПОХІДНІ ТІАЗОЛУ/ТІАЗОЛІДИНОНУ ЯК НОВІ КЛАСИ ГЕТЕРОЦИКЛІЧНИХ СПОЛУК З НОВИМИ МЕХАНІЗМАМИ РЕАЛІЗАЦІЇ ПРОТИПУХЛИННОЇ АКТИВНОСТІ |
| title | ПОЛІФУНКЦІОНАЛЬНІ ПОХІДНІ ТІАЗОЛУ/ТІАЗОЛІДИНОНУ ЯК НОВІ КЛАСИ ГЕТЕРОЦИКЛІЧНИХ СПОЛУК З НОВИМИ МЕХАНІЗМАМИ РЕАЛІЗАЦІЇ ПРОТИПУХЛИННОЇ АКТИВНОСТІ |
| title_alt | Polyfunctional Thiazole/Thiazolidinone Derivatives as a New Class of Heterocyclic Compounds with Novel Mechanisms of Anticancer Activity |
| title_full | ПОЛІФУНКЦІОНАЛЬНІ ПОХІДНІ ТІАЗОЛУ/ТІАЗОЛІДИНОНУ ЯК НОВІ КЛАСИ ГЕТЕРОЦИКЛІЧНИХ СПОЛУК З НОВИМИ МЕХАНІЗМАМИ РЕАЛІЗАЦІЇ ПРОТИПУХЛИННОЇ АКТИВНОСТІ |
| title_fullStr | ПОЛІФУНКЦІОНАЛЬНІ ПОХІДНІ ТІАЗОЛУ/ТІАЗОЛІДИНОНУ ЯК НОВІ КЛАСИ ГЕТЕРОЦИКЛІЧНИХ СПОЛУК З НОВИМИ МЕХАНІЗМАМИ РЕАЛІЗАЦІЇ ПРОТИПУХЛИННОЇ АКТИВНОСТІ |
| title_full_unstemmed | ПОЛІФУНКЦІОНАЛЬНІ ПОХІДНІ ТІАЗОЛУ/ТІАЗОЛІДИНОНУ ЯК НОВІ КЛАСИ ГЕТЕРОЦИКЛІЧНИХ СПОЛУК З НОВИМИ МЕХАНІЗМАМИ РЕАЛІЗАЦІЇ ПРОТИПУХЛИННОЇ АКТИВНОСТІ |
| title_short | ПОЛІФУНКЦІОНАЛЬНІ ПОХІДНІ ТІАЗОЛУ/ТІАЗОЛІДИНОНУ ЯК НОВІ КЛАСИ ГЕТЕРОЦИКЛІЧНИХ СПОЛУК З НОВИМИ МЕХАНІЗМАМИ РЕАЛІЗАЦІЇ ПРОТИПУХЛИННОЇ АКТИВНОСТІ |
| title_sort | поліфункціональні похідні тіазолу/тіазолідинону як нові класи гетероциклічних сполук з новими механізмами реалізації протипухлинної активності |
| topic | тіазол тіазолідинон протипухлинна активність біологічні мішені гібридні молекули |
| topic_facet | тіазол тіазолідинон протипухлинна активність біологічні мішені гібридні молекули thiazole thiazolidinone antitumor activity biotargets hybrid molecules |
| url | https://exp-oncology.com.ua/index.php/Exp/article/view/612 |
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