Syntheses of Bioactive Organoselenium Compounds and Evaluation of Their Anti-Cancer and Antioxidant Activities
No Thumbnail Available
Date
2021
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
The thesis described above deals with the synthesis of novel organoselenocyanates and evaluation of their activity as antioxidants and anti-proliferative agents. As an introduction to the thesis in Chapter 1, a general background on cancer and carcinogenesis leading to cancer development, preventive and treatment options is provided. Relevant literature evidences of important organoselenium compounds as potential chemopreventive/therapeutic agents are also discussed here. Following the literature, a series of benzylic selenocyanates have been developed in Chapter 2 which are inspired from previously known benzyl selenocyanates such as p-XSC, having promising chemopreventive properties. The compound bearing three selenocyanate functionalities was identified as the most effective compound against MDA-MB-231 cells and also MCF-7 and T-47D cells while being relatively less toxic to normal cells. Furthermore, the same compound arrested the cancer cells at S phase of the cell cycle, inhibited cellular migration, and showed favourable drug-like properties suggesting that increasing the number of selenocyanate functionalities in a single molecule enhances the anti-proliferative activity of the compound against triple-negative cancer cells. Chapter 3 describes synthesis of additional substituted benzyl selenocyanates as well as 1,2,3-triazole and 2,4-thiazolidine-1,3-dione-containing selenocyanates which also showed significant anti-cancer activities. Compounds bearing 1,2,3-triazole moiety, displayed prominent cytotoxicity against both MDA-MB-231 cells and normal HEK-293 cells, therefore showing lesser selectivity towards cancer cells. Contrastingly, 4-nitrobenzyl selenocyanate showed higher selectivity towards MDA-MB-231 cells. The same compound was found to be responsible for S-phase cell-cycle arrest and downregulation of anti-apoptotic, cell survival and anti-inflammatory proteins such as bcl-2, survivin and COX-2 respectively. Chapter 4 reports development of benzimidazole- and imidazole-based ionic selenocyanates and the corresponding selenazolium and selenazinium selenocyanates and evaluation of their antioxidant activities. Finally, Chapter 5 reports synthesis of additional set of benzimidazole-based selenazolium and
selenazinium selenocyanates having a 4-substituted phenyl moiety and a newer class of C2-phenyl substituted benzimidazole-based open chain ionic and neutral selenocyanates. The compounds developed in chapters 4 and 5 were evaluated for their anti-cancer activities similar to as reported in chapter 2; 4-NO2-substituted benzimidazole based neutral selenocyanate was identified as the best compound against MDA-MB-231 cells.
Description
Supervisor: Bhabak, Krishna Pada
Keywords
Organoselenium, Antioxidant, Anti-cancer