Design and synthesis of coumarin-triazole hybrids: biocompatible anti-diabetic agents, in silico molecular docking and ADME screening

Natural products have been extensively explored for their role in drug design and development to eradicate numerous types of diseases. Also, heterocycles‐based motifs are known to possess a wide range of therapeutic applications. Among them, pyrazole is a well‐exploited scaffold by researchers in the different fields of medicinal chemistry. Recently, pharmacophoric hybridization became most urged approach in which two biologically active pharmacophoric skeletons tend to fuse together in any structural portion. Hence, pyrazole and its cyclic bio‐isosteres may clubbed together to design and develop novel potent molecules against clinical disorders with least toxicity profile. In the present review, we aim to compile the numerous recent advancements in the medicinal chemistry of natural metabolites containing pyrazole and its bio‐isosteres hybrid compounds with the following objectives: (1) To summarize the recent literature reports of last six years that are focused on the biological potential of natural pyrazole and its bio‐isosteres hybrid derivatives; (2) To deliberate current developments in the medicinal aspect of natural compounds through their structural alteration by introducing pyrazole and its cyclic analogues; (3) To emphasize the complete correlation between structure activity relationship (SAR) and therapeutic response to disclose productive concepts for the generation of potential semi‐synthetic candidates.

Section: Recent Advances In Natural Metabolites Linked Pyrazole or It...mentioning

confidence: 59%

Therapeutic Potential of Natural Metabolites Coupled Pyrazole and Its Bio‐Isosteres: Medicinal Perspectives and SAR Studies

Nehra,

Kumar,

Chawla

et al. 2024

“…The distances to the nearest nuclei outside and inside the surface from the Hirshfeld surface are d e and d i , respectively. The computed volume inside the Hirshfeld surface is 451.61 Å 3 in a 422.84 Å 2 area [58,60–63] …”

Section: Resultsmentioning

confidence: 99%

“…The computed volume inside the Hirshfeld surface is 451.61 Å 3 in a 422.84 Å 2 area. [58,[60][61][62][63] The quantitative contributions of molecular interactions to the overall Hirshfeld surface are determined by analysing the 2D fingerprint plot. The H…H (27.9 %) contacts has maximum and O…N (0.1 %) has minimum contributions.…”

Section: Hirshfeld Surface Studiesmentioning

confidence: 99%

Microwave‐Assisted Synthesis and Characterization of Some Aldehyde Derivatives of Imidazo[2,1‐b][1,3,4]thiadiazole: Crystal Structure Insights, In‐Silico and Biological Studies

Sagar,

Kumara,

et al. 2023

Self Cite

The microwave‐assisted synthesis, crystallographic studies, in‐silico docking and the evaluation of in‐vitro biological activities of 2‐(3,4‐dimethoxy)‐6‐(substituted phenyl)‐ imidazo[2,1‐b][1,3,4]thiadiazole‐5‐carbaldehydes is represented here. Single‐crystal X‐ray diffraction experiments were used to identify the crystal structure of the 6‐(4‐chlorophenyl)‐2‐(3,4‐dimethoxybenzyl)imidazo[2,1‐b][1,3,4]thiadiazole‐5‐carbaldehyde. Using fingerprint plots, Hirshfeld surface analysis was used to confirm the contributions of distinct intermolecular interactions in the development of the crystal packing. Further, density functional theory calculations were employed to calculate the molecule's electronic properties. The chemically active regions on the molecule are identified by analysing the molecular electrostatic potential map. in‐silico studies revealed that the molecules can be effectively used as antibacterial agents by taking the 3q82 receptor with chloramphenicol as a standard. As compared to the chloramphenicol standard, in‐vitro tests showed that molecules 4 a, 4 b, 4 c, and 4 f had a zone of inhibition that ranged from 9 to 11 mm against both Gram‐positive (Bacillus subtilis) and Gram‐negative (Escherichia coli) bacteria. The minimum inhibitory concentration was between 40 to 70 μg/ml. These compounds′ Hydroxyl free radical scavenging activity was between 40 to 85 %. Whereas, DPPH radical scavenging activity was between 40 and 70 %. Percentage hemolysis or cell protective activity of the compounds was ineffective at 20–40 %.

“…The hormone insulin, produced by the pancreas, plays an important role in transporting glucose from the blood to the cells for easy storage and use as an energy source when insulin is insufficient or when insulin production is unsustainable of glucose inside the cell. Notably, there has been a clear increase in the incidence of diabetes in the younger population [1] Factors contributing to this increase include dietary and lifestyle choices, as well as hereditary influences. Common signs and symptoms of diabetes include overeating, weight loss, heart disease, kidney failure, hearing loss, and bacterial and fungal skin infections [2] and also diabetes can give mood in the 1990s.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 7‐{[2‐(4‐ substituted phenyl)‐2‐oxoethyl] amino}‐4‐methyl‐2H‐1‐benzopyran‐2‐one derivatives and evaluation of their pharmacological activities

Megha,

Bodke

2024

In this study, a novel series of 7‐[2‐(4‐substituted)‐2‐oxoethyl]amino‐4‐methyl‐2H‐1‐benzopyran‐2‐one derivatives (3 a‐f) were synthesized using 7‐amino‐4‐methyl coumarin and p‐substituted phenacyl bromides, and their pharmacological effects were examined. This reaction was carried out with potassium carbonate as a catalyst in dimethylformamide for 24 h at ambient temperature. The structures of synthesized compounds have been characterized by analysis using FTIR, NMR (1H and 13C) and Mass spectroscopic techniques, and their antibacterial, antidiabetic, and anti‐inflammatory properties have been explored. All synthesized compounds have exhibited good antibacterial activity against S. aureus, B. substilis, E. coli, and S. typhi.Compound 3 f shows maximum activity (zone of inhibition) at a 12 g/mL concentration compared to others. Compounds 3 c and 3 f showed excellent α‐amylase activity and had the lowest IC50 values for α‐glucosidase enzyme activities. The least IC50 value (12.42±0.27 g/mL) was demonstrated by the 3 e compound, which exhibited potent anti‐inflammatory activities. in silico Molecular docking studies suggested that compounds 3 f and 3 a interacted effectively with 4DO3: FAAH and 5DI1: MAP4 K4 proteins with good binding energies of −10.3 and −9.5 Kcal/mol, respectively.