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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]

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]

Excitotoxicty, a key pathogenic event is characteristic of the onset and development of neurodegeneration. The glutamatergic neurotransmission mediated through different glutamate receptor subtypes plays a pivotal role in the onset of excitotoxicity. The role of NMDA receptor (NMDAR), a glutamate receptor subtype, has been well established in the excitotoxicity pathogenesis. NMDAR overactivation triggers excessive calcium influx resulting in excitotoxic neuronal cell death. In the present study, a series of benzazepine derivatives, with the core structure of 3-methyltetrahydro-3 H-benzazepin-2-one, were synthesised in our laboratory and their NMDAR antagonist activity was determined against NMDA-induced excitotoxicity using SH-SY5Y cells. In order to assess the multi-target-directed potential of the synthesised compounds, Aβ aggregation inhibitory activity of the most potent benzazepines was evaluated using thioflavin T (ThT) and Congo red (CR) binding assays as Aβ also imparts toxicity, at least in part, through NMDAR overactivation. Furthermore, neuroprotective, free radical scavenging, anti-oxidant and anti-apoptotic activities of the two potential test compounds ( 7 and 14) were evaluated using primary rat hippocampal neuronal culture against Aβ-induced toxicity. Finally, in vivo neuroprotective potential of 7 and 14 was assessed using intracerebroventricular (ICV) rat model of Aβ-induced toxicity. All of the synthesised benzazepines have shown significant neuroprotection against NMDA-induced excitotoxicity. The most potent compound ( 14) showed relatively higher affinity for the glycine binding site as compared with the glutamate binding site of NMDAR in the molecular docking studies. 7 and 14 have been shown experimentally to abrogate Aβ aggregation efficiently. Additionally, 7 and 14 showed significant neuroprotective, free radical scavenging, anti-oxidant and anti-apoptotic properties in different in vitro and in vivo experimental models. Finally, 7 and 14 attenuated Aβ-induced tau phosphorylation by abrogating activation of tau kinases, i.e. MAPK and GSK-3β. Thus, the results revealed multi-target-directed potential of some of the synthesised novel benzazepines against excitotoxicity. [ABSTRACT FROM AUTHOR]

The benzazepine ring system has offered interesting CNS-active medicinal agents. Taking this privileged structure as the basic scaffold, $$\hbox {C}_{1}$$ and/or $$\hbox {N}_{3}$$ -alkylated benzazepin-2-one derivatives and their reduced analogs have been prepared as potential $$\hbox {5-HT}_{\mathrm{2C}}$$ receptor agonists. The selective alkylation at the $$\hbox {C}_{1}$$ and/or $$\hbox {N}_{3}$$ positions of this seven-membered lactam ring is here reported for the first time under different reaction conditions. The synthesized compounds were evaluated for their biological profile as potential $$\hbox {5-HT}_{\mathrm{2C}}$$ agonists using a classic pharmacological approach. Three derivatives ( 15, 17, and 20) have shown promising $$\hbox {5-HT}_{\mathrm{2C}}$$ agonistic activity which can be further optimized as anti-obesity agents for the treatment of male sexual dysfunction. Further, a homology model for $$\hbox {5-HT}_{\mathrm{2C}}$$ receptor was generated using MODELLER, and ligand-receptor interactions for these potential molecules were studied. [ABSTRACT FROM AUTHOR]