synthesis and evaluation of dimethyl tin 4-cyclohexyl thiosemicarbazone as a novel antitumor age

• Published in: Experimental Oncology
• Date: 2009
• Main Authors: Sen, A., Chaudhuri, T.K.
• Format: Article
• Language: English
• Published: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2009
• Subjects: Original contributions
• Online Access: https://nasplib.isofts.kiev.ua/handle/123456789/135103
• Journal Title: Digital Library of Periodicals of National Academy of Sciences of Ukraine
• Cite this: synthesis and evaluation of dimethyl tin 4-cyclohexyl thiosemicarbazone as a novel antitumor age / A. Sen, T.K. Chaudhuri // Experimental Oncology. — 2009. — Т. 31, № 1. — С. 22-26. — Бібліогр.: 24 назв. — англ.

Aim: To develop a rationally designed new organotin compound namely dimethyl tin 4-cyclohexyl thiosemicarbazone (D4-t) and
 evaluate its putative antitumor activity. Methods: Starting from 4-cyclohexyl thiosemicarbazone, a three step synthetic procedure was
 followed to obtain the title compound. In vivo lymphocyte activation property of the compound at three different doses was assayed
 by measuring the blastogenesis. Concanavalin A (ConA) was used as standard mitogen for murine T cells stimulation in vivo. Also,
 the synthesis of DNA by the activated lymphocytes was measured after injecting the D4-t. The lymphocyte activation property and
 antitumor efficacy of D4-twere assessed inSarcoma-180 (S-180) bearing mice. The organization of lymphoid cells was studied in the
 histological preparations ofspleen and mesenteric lymph node. Tumor neutralization assay (Winn assay) was conducted to examine
 whether immune responses were associated with the manifestation of antitumor efficacies of this compound in S-180 in vivo. The
 DNA synthesis inhibitory effect of the compound in S-180 cells was studied in vitro, and was found significant (P < 0.001). Results:
 Different doses of the new compound caused differential response of blastogenesis and DNA synthesis. In comparison to ConA, the
 title compound showed a good number of blast cells at its optimum dose of 5 mg/kg. It caused maximum synthesis of DNA by the
 lymphoid cells. In histological preparations, the gradual transformation of lymphocytes into blasts was observed without any visible
 toxicity. Winn assay revealed that 5 mg/kg of D4-t was able to reduce tumor mass without severe toxicity. This organotin compound
 also inhibits the synthesis of DNA in S-180 tumor cells in comparison to Platin10 and ConA. Conclusion: The title compound has
 the lymphocyte activation property and stimulates immune response of the lymphoid cells, which in turn express the antitumor
 activity without any significant toxicity. Results indicate promising therapeutic potential of D4-t.