In the present study, a series of 2,3-dihydro-1,5-benzothiazepine derivatives 1B – 14B has been synthesized sand characterized by various spectroscopic techniques. The enzyme inhibitory activities of the target analogues were assessed using in vitro and in vivo mechanism-based assays. The tested compounds 1B – 14B exhibited in vitro inhibitory potential against α-glucosidase with IC 50 = 2.62 ± 0.16 to 10.11 ± 0.32 μM as compared to the standard drug acarbose (IC 50 = 37.38 ± 1.37 μM). Kinetic studies of the most active derivatives 2B and 3B illustrated competitive inhibitions. Based on the α-glucosidase inhibitory effect, the compounds 2B , 3B , 6B , 7B , 12B , 13B , and 14B were chosen in vivo for further evaluation of antidiabetic activity in streptozotocin-induced diabetic Wistar rats. All these evaluated compounds demonstrated significant antidiabetic activity and were found to be nontoxic in nature. Moreover, the molecular docking study was performed to elucidate the binding interactions of most active analogues with the various sites of the α-glucosidase enzyme (PDB ID 3AJ7 ). Additionally, quantitative structure–activity relationship (QSAR) studies were performed based on the α-glucosidase inhibitory assay. The value of correlation coefficient ( r ) 0.9553 shows that there was a good correlation between the 1B – 14B structures and selected properties. There is a correlation between the experimental and theoretical results. Thus, these novel compounds could serve as potential candidates to become leads for the development of new drugs provoking an anti-hyperglycemic effect.

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We herein report a design and synthesis of new 1,3,5-triazine based pyrazole derivatives (5a-i) for anticancer activity targeting epidermal growth factor (EGFR) tyrosine kinase. The newly synthesized compounds were characterized...

(E)-N-(3-(1-(2-(4-(2,2,2-Trifluoroacetamido)benzoyl)hydrazono)ethyl)phenyl)nicotinamide (compound 10) was designed as an antiangiogenic VEGFR-2 inhibitor with the essential pharmacophoric structural properties to interact with the catalytic pocket of VEGFR-2. The designed derivative was synthesized, and its structure was confirmed through Ms, elemental, 1H, and 13C spectral data. The potentiality of the designed pyridine derivative to bind with and inhibit the vascular endothelial growth factor receptor-2 (VEGFR-2) enzyme was indicated by molecular docking assessments. In addition, six molecular dynamic (MD) experiments proved its correct binding with VEGFR-2 over 100 ns. Additionally, the molecular mechanics energies, combined with the generalized born and surface area (MM-GBSA) analysis, identified the precise binding with optimum energy. To explore the stability and reactivity of the designed pyridine derivative, density functional theory (DFT) calculations, including electrostatic potential maps and total electron density, were carried out. Additionally, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis demonstrated its general likeness and its safety. The designed compound was synthesized to evaluate its effects against VEGFR-2 protein, cancer, and normal cells. The in vitro results were concordant with the in silico results, because the new pyridine derivative (compound 10) displayed VEGFR-2 inhibition with an IC50 value of 65 nM and displayed potent cytotoxic properties against hepatic (HepG2) and breast (MCF-7) cancer cell lines with IC50 values of 21.00 and 26.10 μM, respectively; additionally, it exhibited high selectivity indices against the normal cell lines (W-38) of 1.55 and 1.25, respectively. The obtained results present compound 10 as a new lead VEGFR-2 inhibitor for further biological investigation and chemical modifications.