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Cancer chemotherapy has been shifted from conventional cytotoxic drug therapy to selective and target-specific therapy after the findings about DNA changes and proteins that are responsible for cancer. A large number of newer drugs were discovered as targeted therapy for particular types of neoplastic disease. The initial discovery includes the development of the first in the category, imatinib, a Bcr-Abl tyrosine kinase inhibitor (TKI) for the treatment of chronic myelocytic leukemia in 2001. But the joy did not last for long as the drug developed a point mutation within the ABL1 kinase domain of BCR-ABL1, which subsequently led to the discovery of many other TKIs. Resistance was observed for newer TKIs a few years after their launching, but the use of TKIs in life-threatening cancer therapy is considered as far better compared with the risks of disease because of its target specificity and hence less toxicity. In search of a better anticancer agent, the physiochemical properties of the lead molecule have been modified for its efficacy toward disease and delay in the development of resistance. Deuteration in the drug molecule is one of such modifications that alter the pharmacokinetic properties, generally its metabolism, as compared with its pharmacodynamic effects. Precision deuteration in many anticancer drugs has been carried out to search for better drugs for cancer. In this review, the majority of anticancer drugs and molecules for which deuteration was applied to get better anticancer molecules were discussed. This review will provide a complete guide about the benefits of deuteration in cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Polycystic Ovary Syndrome (PCOS) is a widespread and complex hormonal disorder occurs in women of reproductive age, characterized by hormonal imbalances and ovarian dysfunction. Current approaches to treating PCOS often address specific symptoms, highlighting the demand for innovative therapeutic agents that can tackle its multifaceted nature. The present study endeavors to investigate the potential of new chromen‐2‐one derivatives in the management of PCOS. A total of 30 derivatives have been synthesized and evaluated for their in vitro inhibitory effects on 5‐α reductase and antioxidant activities. Based on the promising in vitro activity and acute toxicity profile of 4‐methoxy‐N‐(3‐(4‐methoxyphenyl)‐2‐oxo‐2H‐chromen‐6‐yl) benzamide (29), it was selected for subsequent in vivo investigation in experimental animal models of PCOS. The study also includes molecular interaction analysis through docking and dynamic studies of compound (29). [ABSTRACT FROM AUTHOR]

• A series of carbazole-stilbene hybrids were synthesized as anti-AD agents. • Compound (50) exhibited good inhibitory activities against AChE and BuChE. • Compound (50) showed notable inhibition of self-mediated Aβ 1–42 aggregation. • It also possessed specific copper ion chelation property. Molecules capable of engaging with multiple targets associated with pathological condition of Alzheimer's disease have proved to be potential anti-Alzheimer's agents. In our goal to develop multitarget-directed ligands for the treatment of Alzheimer's disease, a novel series of carbazole-based stilbene derivatives were designed by the fusion of carbazole ring with stilbene scaffold. The designed compounds were synthesized and evaluated for their anti-AD activities including cholinesterase inhibition, Aβ aggregation inhibition, antioxidant and metal chelation properties. Amongst them, (E)-1-(4-(2-(9-ethyl-9 H -carbazol-3-yl)vinyl)phenyl)-3-(2-(pyrrolidin-1-yl)ethyl)thiourea (50) appeared to be the best candidate with good inhibitory activities against AChE (IC 50 value of 2.64 μM) and BuChE (IC 50 value of 1.29 μM), and significant inhibition of self-mediated Aβ 1–42 aggregation (51.29% at 25 μM concentration). The metal chelation study showed that compound (50) possessed specific copper ion chelating property. Additionally, compound (50) exhibited moderate antioxidant activity. To understand the binding mode of 50 , molecular docking studies were performed, and the results indicated strong non-covalent interactions of 50 with the enzymes in the active sites of AChE, BuChE as well as of the Aβ 1-42 peptide. Additionally, it showed promising in silico ADMET properties. Putting together, these findings evidently showed compound (50) as a potential multitarget-directed ligand in the course of developing novel anti-AD drugs. [ABSTRACT FROM AUTHOR]

Review: 240 refs. [ABSTRACT FROM AUTHOR]