Glucokinase (GK) is the key enzyme expressed in β-cells of pancreas and liver hepatocytes and helps in the maintenance of blood glucose levels in normal range. Activators of GK are the novel category of drug candidates which activate GK enzyme allosterically and show their antidiabetic activity. A new series of 3,5-disubstituted benzamide analogues was designed, synthesized and evaluated as GK activators by in vitro assay as well as in silico docking studies followed by evaluation of antihyperglycemic activity in animal model. Amongst the synthesized derivatives, compounds 5c, 5f, 5i, 6c, 6e and 6h displayed excellent in vitro GK activation. Compounds 6c and 6e exhibited highest antihyperglycemic activity in oral glucose tolerance test in animal model. Compound 6e displayed most significant antihyperglycemic activity and comparable to that of standard drug in animal studies. In addition, antihyperglycemic activity of the synthesized molecules was further supported by the in silico docking studies of the synthesized derivatives in the allosteric site of GK protein.

Serotoninergic signaling is identified as a crucial player in psychiatric disorders (notably depression), presenting it as a significant therapeutic target for treating such conditions. Inhibitors of serotoninergic signaling (especially selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI)) are prominently selected as first-line therapy for the treatment of depression, which benefits via increasing low serotonin levels and norepinephrine by blocking serotonin/norepinephrine reuptake and thereby increasing activity. While developing newer heterocyclic scaffolds to target/modulate the serotonergic systems, imidazole-bearing pharmacophores have emerged. The imidazole-derived pharmacophore already demonstrated unique structural characteristics and an electron-rich environment, ultimately resulting in a diverse range of bioactivities. Therefore, the current manuscript discloses such a specific modification and structural activity relationship (SAR) of attempted derivatization in terms of the serotonergic efficacy of the resultant inhibitor. We also featured a landscape of imidazole-based development, focusing on SAR studies against the serotoninergic system to target depression. This study covers the recent advancements in synthetic methodologies for imidazole derivatives and the development of new molecules having antidepressant activity via modulating serotonergic systems, along with their SAR studies. The focus of the study is to provide structural insights into imidazole-based derivatives as serotonergic system modulators for the treatment of depression.

Anticancer is the high priority research area for the scientists as cancer is one the leading causes of deaths globally. It is pertinent to mention here that the conventional anticancer drugs such as methotrexate, vincristine, cyclophosphamide, etoposide, doxorubicin, cisplatin etc. are not much efficient for treatment of different types of cancer; also suffer from serious side effects leading to therapy failure. A large variety of cancer related receptors such as carbonic anhydrase, tyrosine kinase, topoisomerase, protein kinase, histone deacetylase etc. have been identified which can be targeted by anticancer drugs. Heterocycles like oxadiazole, thiazole, thiadiazole, indole, pyridine, pyrimidine, benzimidazole etc. play pivotal role in modern medicinal chemistry because they have broad spectrum of pharmacological activities including prominent anticancer activity. Therefore, it was considered significant to explore heterocyclic compounds reported in recent most literature which can bind effectively with the cancer related receptors. This will not only provide targeted approach to deal with cancer but also safety profile of the drugs can be further improved. The information provided in this manuscript may be found useful for drug design and development of anticancer drugs.

Computer-aided drug design is a powerful and promising tool for drug design and development, with a reduced cost and time. In the current study, we rationally selected a library of 34 fused imidazo[1,2-a]quinoxaline derivatives and performed virtual screening, molecular docking, and molecular mechanics for a lead identification against tubulin as an anticancer molecule. The computational analysis and pharmacophoric features were represented as 1A2; this was a potential lead against tubulin, with a maximized affinity and binding score at the colchicine-binding site of tubulin. The efficiency of this lead molecule was further identified using an in vitro assay on a tubulin enzyme and the anticancer potential was established using an MTT assay. Compound 1A2 (IC₅₀ = 4.33–6.11 µM against MCF-7, MDA-MB-231, HCT-116, and A549 cell lines) displayed encouraging results similar to the standard drug colchicine in these in vitro studies, which further confirmed the effectiveness of CADD in new drug developments. Thus, we successfully applied the utility of in silico techniques to identify the best plausible leads from the fused azaheterocycles.

Oriental Journal of Chemistry is a peer reviewed quarterly research journal of pure and applied chemistry. It publishes standard research papers in almost all thrust areas of current chemistry of academic and commercial importance. It provides a platform for rapid publication of quality research papers, reviews and chemistry letters. Oriental Journal of Chemistry is abstracted and indexed in almost all reputed National and International agencies.