Vishnu Ashok Adole

We have investigated synthesis, spectral analysis, and DFT calculations of β‐amino‐crotonate‐based novel 1,2,4‐triazole derivatives (3A‐3I) with antidiabetic activities. Research published between 2018 and 2025 shows that triazole coupled with heterocyclic ring structures has promising dual enzyme inhibition moderate for antidiabetic effects. The compound 3B containing fluorine group at para position of aryl ring demonstrated moderate α‐amylase activity, similarly, with an IC ₅₀ value of 65.74 µg/mL. The compound 3A containing chlorine at the ortho position of aryl ring exhibited the moderate α‐amylase inhibitory activity. The compounds 3B and 3A exhibited good in vitro α‐glucosidase inhibitory activities with an IC ₅₀ value of 76.48 and 77.31 µg/mL, respectively, as compare to other compounds and acarbose. In silico studies revealed that compound 3B interacts with three enzyme active site hydrogen bonds. In vivo results showed that the analysis of glucose levels in the hemolymph homogenate revealed that the fly group treated with acarbose exhibited a considerable reduction in glucose levels compared to the control group. These findings were showed that triazole‐derived crotonate moiety function as α‐amylase α‐glucosidase enzyme inhibitors, which aid in the development of new treatments for diabetes mellitus and can serve as lead molecules in drug discovery as possible antidiabetic medicines.

A series of ( E )‐4‐(aryl)‐2‐(2‐((1,3‐diphenyl‐1 H ‐pyrazol‐4‐yl)methylene)hydrazineyl)thiazoles ( 4a – 4d ) were synthesized via the condensation of 1,3‐diphenyl‐1 H ‐pyrazole‐4‐carbaldehyde, thiosemicarbazide, and phenacyl bromide derivatives in ethanol using acetic acid as a catalyst, affording high yields (>80%). Structural characterization was confirmed through FT IR and ¹ H NMR analyses. The antiinflammatory activity evaluated by egg albumin denaturation assay demonstrated a dose‐dependent inhibition trend. Compound 4d exhibited the highest inhibition (32.6 ± 1.91% at 100 µg/mL) compared to 4c (12.7 ± 0.25%), 4b (7.37 ± 0.49%), and 4a (7.14 ± 1.03%) in comparison with the standard drug (44.76 ± 1.08%). Molecular docking against COX‐2 revealed strong binding affinities, with docking scores ranging from –10.9 to –11.5 kcal/mol. Compound 4a showed the strongest binding through hydrophobic and π–π stacking interactions. Absorption, distribution, metabolism, and excretion (ADME) predictions suggested favorable pharmacokinetic profiles, with all compounds. DFT analysis revealed HOMO–LUMO energy gaps ranging from 3.903 to 3.989 eV, confirming chemical stability and reactivity. MESP plots revealed electrophilic and nucleophilic contacts in the synthesized compounds.

1. The global surge in antimicrobial resistance poses a critical threat to public health, undermining the effectiveness of existing antibiotics and rendering standard treatments increasingly ineffe...

Breast cancer remains one of the most pressing global health concerns, emphasizing the urgent need for novel and effective therapeutic strategies. In this context, a new series of quinolinyl-thiazole derivatives incorporating an N-methyl piperazine moiety (6a–6h) was rationally designed, synthesized, and thoroughly characterized using FT-IR, ¹H NMR, ¹³C NMR, and mass spectral methods. The anti-breast cancer potential of these compounds was assessed against the triple-negative breast cancer cell line MDA-MB-231, exhibiting IC₅₀ values ranging from 1.415 ± 0.16 to 2.898 ± 0.27 µM, thus highlighting their anti-breast cancer potential. Within the series, compound 6a showed the highest potency with the lowest IC₅₀ value, whereas 6f displayed the weakest activity. Molecular docking of quinolinyl–thiazole derivatives (6a, 6f, 6g and 6h) against epidermal growth factor receptor tyrosine kinase revealed binding affinities correlating with their in vitro cytotoxicity on MDA-MB-231 cells, with 6a showing the strongest activity (IC₅₀ = 1.415 ± 0.16 µM; docking score = −10.0 kcal mol⁻¹) via key hydrogen bonds, electrostatic contacts, and hydrophobic interactions. Furthermore, in silico ADME evaluation and drug-likeness analysis indicated that all synthesized derivatives possessed favorable pharmacokinetic properties. Density functional theory analysis of the most potent compound (6a) offered valuable insights into its structural characteristics, electronic distribution, and chemical reactivity via optimized geometry, frontier molecular orbital and molecular electrostatic potential surface studies. The results suggested that the synthesized compounds are promising candidates for further investigation.

In this study, two pyrazole-based hydrazone derivatives, 5-methyl-1-phenyl-4-(1-(2-phenylhydrazineylidene)ethyl)-1H-pyrazole (PMPH) and 1-(4-fluorophenyl)-5-methyl-4-(1-(2-phenylhydrazineylidene)ethyl)-1H-pyrazole (4 F-PMPH), were synthesized and the structures of the compounds were elucidated through FT-IR, ¹H and ¹³C NMR, and mass spectral methods. The anti-inflammatory potential was evaluated using the bovine serum albumin denaturation assay, with PMPH and 4 F-PMPH showing maximum inhibition at 0.5 mg/mL, respectively, suggesting that fluorine substitution enhances bioactivity. Molecular docking studies against COX-II (PDB: 3LN1) revealed favorable binding energies of − 7.21 kcal/mol (PMPH) and − 8.03 kcal/mol (4 F-PMPH). Molecular dynamics simulation of the best docked compound 4 F-PMPH with COX-II (PDB: 3LN1) revealed a stable complex over a 100 ns simulation, supporting its potential as a promising inhibitor. In silico ADME analyses revealed pharmacokinetic behavior and drug-likeness. A comparative Density functional theory-based spectroscopic and electronic investigation was conducted using the B3LYP/6-31G(d,p) level of theory. Vibrational frequency analysis showed strong correlation between theoretical and experimental IR spectra. Frontier molecular orbital analysis, molecular electrostatic surface potential maps, Mulliken charges, electronic and global reactivity parameters were also studied. Besides, reduced density gradient, non-covalent interaction, electron localization function, and localized orbital locator maps were analyzed for both the compounds.

A thiazole–thiophene derivative, (E)-4-(2-(2-(1-(5-chlorothiophen-2-yl)ethylidene)hydrazinyl)thiazol-4-yl)benzonitrile (CTHTBN), was synthesized via a one-pot multicomponent reaction involving 5-chloro-2-acetylthiophene, thiosemicarbazide, and 4-(2-bromoacetyl)benzonitrile. The synthesized compound was characterized by FT-IR, ¹H NMR, and ¹³C NMR spectroscopy, confirming the formation of the title compound. Density Functional Theory (DFT) calculations at the B3LYP/6-311G(d,p) level were performed to explore the electronic structure and reactivity of CTHTBN. The HOMO and LUMO energies were found to be −5.75 eV and −2.03 eV, respectively, with an energy gap (E_g) of 3.72 eV, suggesting a balanced chemical stability and reactivity. The dipole moment of 7.9381 Debye indicated substantial polarity, favorable for biological interactions. Global reactivity descriptors, including chemical hardness (η = 1.86 eV), chemical softness (σ = 0.5376 eV⁻¹), electronegativity (χ = 3.89 eV), electrophilicity index (ω = 4.07 eV), and maximum charge transfer capacity (ΔN_max = 2.09), further supported the molecule’s electronic competence. Molecular docking against M. tuberculosis CYP51 revealed a strong binding affinity (−8.8 kcal/mol), stabilized by π–sulfur contacts with MET79 and PHE83, π–π stacking with TYR76, and π–π T-shaped interactions with PHE83 and the heme cofactor. Additional π–alkyl interactions with LEU321, ALA325, and the heme group reinforced hydrophobic complementarity, confirming efficient accommodation of CTHTBN in the active site. These findings suggest that CTHTBN holds promising potential as an antimycobacterial agent targeting CYP51 and may be explored in future biological studies.