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Tuberculosis (TB) remains a global health concern, necessitating the continuous search for novel therapeutic agents to combat drug-resistant strains and enhance treatment efficacy. The present study focuses on designing, synthesizing, and exploring quinoline analogues as potential anti-tubercular agents. Quinoline scaffolds like bedaquiline inhibit the ATP synthase enzyme involved in energy production. A diverse library of 19 quinoline derivatives was sys tematically synthesized through rational structural modifications. The quinoline analogues were evaluated for their anti-tubercular activity against Mycobacterium tuberculosis (M.tb). Furthermore, the study delves into the molecular interactions between the synthesized quinoline derivatives and M.tb ATP synthase, shedding light on the underlying mechanisms of their anti-tubercular activity. The initial in-vitro screening revealed that some of the designed molecules were active against M.tb, making them potential candidates for further development. A diverse library of 19 quinoline derivatives was systematically synthesized through rational structural modifications. Molecular docking studies showed to target the ATP synthase protein of Mycobacterium tuberculosis (MtB). The quinoline analogs were found to have good anti-tubercular activity again Mtb. [ABSTRACT FROM AUTHOR]

Alpha‐amylase plays a crucial role in blood glucose levels, and thus, its inhibitor can be used to control diabetes. Thus, in vitro alpha‐amylase inhibitory activities were studied for synthesized benzoxazole compounds. The 2‐amino‐benzoxazoles were prepared by reacting 2‐aminophenol with cyanogen bromide, which was coupled with phenoxy acetic acid derivatives (6 a‐n). The compound 6 h was found to be significantly active with IC50 values of 348.43 μg/mL against alpha‐amylase compared to acarbose (IC50=682.54 μg/mL). The molecular docking and molecular dynamic simulation showed better affinity and stability of 6 h at the binding site of the alpha‐amylase protein. Further, a preliminary bioevalauation and antidiabetic study were done through in vivo using SD rats. The efficacy study showed a significant improvement in glucose levels, total cholesterol, triglyceride, LDL, and HDL levels in the compound 6 h and was found to be a lead antidiabetic agent. [ABSTRACT FROM AUTHOR]

An efficient and eco-friendly procedure was developed for the synthesis of N -aryl-2-((3-aryl-1,2,4-oxadiazol-5-yl)thio)acetamides from N -aryl-2-thiocyanatoacetamides and substituted N -hydroxybenzimidoyl chlorides that were prepared easily from the commercially available anilines and aryl aldehydes, respectively. The N -aryl-2-thiocyanatoacetamide acts as a dipolarophile while the nitrile oxide formed in situ from substituted N -hydroxybenzimidoyl chloride acts as the nucleophilic partner in a 1,3-dipolar cycloaddition reaction mediated by triethylamine base in ethanol medium. The procedure affords excellent yields of desired products containing electron-withdrawing and electron-donating groups on the aromatic rings, in short reaction time with ease of operation. The procedure for the synthesis of scaffolds that are potentially valuable for their biological properties also offers the possibility of scale-up to higher quantities. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a common factor contributing to cognitive decline in aged people. The etiology of AD involves several mechanisms, including the breakdown of acetylcholine, the accumulation of amyloid beta, the formation of neurofibrillary tangles and inflammation. Several targets have been discovered in the study that are useful in reducing the cognitive decline associated with AD. By employing network pharmacology, molecular docking and MD simulations, we have ascertained that Roemerine can specifically interact with MAO-A. Network pharmacology identified a set of genes with a higher degree of interactions. MAO-A was identified as the gene with the highest interaction level with 37 other genes. MAO-A gene was interconnected with other top 10 genes with overall higher degrees of interactions. Roemerine molecule showed a binding energy of −5.27 kcal/mol, which was better than the reference ligand found to be −4.43 kcal/mol. MD simulations demonstrated that the average RMSD for Roemerine was 4.67 Å, whereas the average RMSF was 1.06 Å. Conversely, the unbound protein and the reference chemical exhibited average RMSD values of 5.57 Å and 5.74 Å, respectively. In addition, the average RMSF values for them were 1.30 Å and 1.00 Å, respectively. Based on these results, it may be inferred that Roemerine can inhibit MAO-A and potentially be used as a lead for AD. Roemerine is a phytoconstituent of Annona senegalensis. Network pharmacology is used to identify the possible target in AD. It can specifically interact with MAO-A. [ABSTRACT FROM AUTHOR]

A cobalt(II) perchlorate hexahydrate coordinated synthesis of dihydropyrimidin‐ones and ‐thiones through sonochemistry is developed. Herein, the reaction was demonstrated as a simple, efficient, and one‐pot method for synthesizing a series of interesting 3,4‐dihydropyrimidin‐2(1H)‐ones. Further, the reaction mechanism was investigated using mass spectrometry and density functional theory calculations suggesting that a Lewis acid character of cobalt(II) perchlorate hexahydrate plays a crucial role in coordinating carbonyl functionalities and stabilizing the polar intermediates like imine–enamine which further led to cyclized dihydropyrimidin‐ones and ‐thiones. This methodology was further explored to synthesize a gram‐scale synthesis of monastrol drug, a kinase inhibitor. [ABSTRACT FROM AUTHOR]

Water is an eco-friendly and economical solvent in organic synthesis. The ultrasound-assisted chemical reactions have proven to produce a better yield than the existing traditional approaches. Flavonol scaffold is widely distributed in nature. Therefore, it becomes very important to explore and develop a newer method for their synthesis. In the present work, we have described the one-pot efficient synthesis of flavonol and its derivatives using the LiOH.H2O and H2O2 system. Herein we utilized an eco-friendly chemistry approach using ultrasound and water as a medium to afford flavonols in good yields. LiOH.H2O was found to be a mild base to generate the chalcone intermediate whereas H2O2 acted as an oxidizing agent to produce a flavonol as revealed by a mechanistic study using mass spectrometry and NMR spectroscopy. This one-pot synthesis of flavonols is an effective alternative to the existing methods with the advantages of utilizing mild base and oxidant, ease in isolation, economical, eco-friendly, and good yields. [ABSTRACT FROM AUTHOR]