Department Of Pharmaceutical Sciences and Natural Products

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    Regulation of thymidylate synthase: an approach to overcome 5-FU resistance in colorectal cancer
    (Springer, 2022-10-29T00:00:00) Kumar, Adarsh; Singh, Ankit Kumar; Singh, Harshwardhan; Thareja, Suresh; Kumar, Pradeep
    Thymidylate synthase is the rate-limiting enzyme required for DNA synthesis and overexpression of this enzyme causes resistance to cancer cells. Long treatments with 5-FU cause resistance to Thymidylate synthase targeting drugs. We have also compiled different mechanisms of drug resistance including autophagy and apoptosis, drug detoxification and ABC transporters, drug efflux, signaling pathways (AKT/PI3K, RAS-MAPK, WNT/? catenin, mTOR, NFKB, and Notch1 and FOXM1) and different genes associated with resistance in colorectal cancer. We can overcome 5-FU resistance in cancer cells by regulating thymidylate synthase by natural products (Coptidis rhizoma), HDAC inhibitors, mTOR inhibitors, Folate antagonists, and several other drugs which have been used in combination with TS inhibitors. This review is a compilation of different approaches reported for the regulation of thymidylate synthase to overcome resistance in colorectal cancer cells. Graphical abstract: [Figure not available: see fulltext.] � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Thiazole and Related Heterocyclic Systems as Anticancer Agents: A Review on Synthetic Strategies, Mechanisms of Action and SAR Studies
    (Bentham Science Publishers, 2022-03-21T00:00:00) Sahil; Kaur, Kamalpreet; Jaitak, Vikas
    Background: Cancer is the second leading cause of death worldwide. Many anticancer drugs are commercially available, but lack of selectivity, target specificity, cytotoxicity, and development of resistance lead to serious side effects. Several experiments have been going on to develop compounds with minor or no side effects. Objective: This review mainly emphasizes synthetic strategies, SAR studies, and mechanism of action if thiazole, benzothiazole, and imidazothiazole-containing compounds as anticancer agents. Methods: Recent literature related to thiazole and thiazole-related derivatives endowed with encouraging anticancer potential is reviewed. This review emphasizes contemporary strategies used for the synthesis of thiazole and related derivatives, mechanistic targets, and comprehensive structural activity relationship studies to provide perspective into the rational design of high-efficiency thiazole-based anticancer drug candidates. Results: Exhaustive literature survey indicated that thiazole derivatives are associated with properties of inducing apoptosis and disturbing tubulin assembly. Thiazoles are also associated with the inhibition of NFkB/mTOR/PI3K/AkT and regulation of estrogenmediated activity. Furthermore, thiazole derivatives have been found to modulate critical targets, such as topoisomerase and HDAC. Conclusion: Thiazole derivatives seem to be quite competent and act through various mechanisms. Some of the thiazole derivatives, such as compounds 29, 40, 62, and 74a with IC50 values of 0.05 ?M, 0.00042 ?M, 0.18 ?M, and 0.67 ?M, respectively, not only exhibit anticancer activity, but they also have lower toxicity and better absorption. Therefore, some other similar compounds could be investigated to aid in the development of anticancer pharmacophores. � 2022 Bentham Science Publishers.
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    Drug Targeting Strategies in Breast Cancer Treatment
    (Bentham Science, 2014) Mayank; Jaitak, Vikas
    Breast cancer (BC) is the leading cause of death among women all over the world. Estrogen receptor (ER) based therapy is one of the major approaches to target BC and is associated with various problems such as primary as well as secondary resistance. ER signaling is a complex pathway as many factors are involved; including several types of ERs and their associated co-regulators. Increasing understanding of ER signals results in new approaches targeting towards BCs. In this context, ER co-regulators have been explored and many modulators of ER co-regulators have been found out. EGFR and mTOR pathways also have significant impact on BC endocrine therapy because of the complex crosstalk mechanism which is responsible for primary and secondary resistance. Triple negative breast cancer (TNBC) is majorly associated with BRCA mutations. Currently there is no approved targeted therapy available in such form of cancer. Although PARP inhibitors seem to be suitable candidates for it. The present review is focused on the current scenario of ER, EGFR, as well as mTOR signaling target therapy. We have also discussed the current status of PARP inhibitors in BC chemotherapy.