Design, synthesis, antimicrobial activity, DFT, and molecular docking studies of pyridine-pyrazole-based dihydro-1,3,4-oxadiazoles against various bacterial and fungal targets.

Antimicrobial resistance which is increasing at an alarming rate is a severe public health issue worldwide. Hence, the development of novel antibiotics is an urgent need as microbes have developed resistance against available antibiotics. In search of novel antimicrobial agents, a convenient route for the preparation of substituted 3-(1-phenyl-3-(p-tolyl)-1H-pyrazol-4-yl)-1-(2-phenyl-5-(pyridin-3-yl)-1,3,4-oxadiazol-3(2H)-yl)prop-2-en-1-ones (6a-6o) has been adopted by using pyridine-3-carbohydrazide and various aromatic aldehydes. The newly synthesized compounds were characterized by using various spectral techniques, for example, IR, 1 H NMR, 13 C NMR, and mass spectroscopy. Synthesized hybrids were studied for in vitro antimicrobial potency against various bacterial and fungal strains. Antibacterial results revealed that compounds 6e, 6h, 6i, 6l, and 6m were found to be most active against bacterial strains as they showed minimum inhibitory concentration (MIC) value of 62.5 µg/mL while compounds 6d, 6e, and 6h showed MIC value of 200 µg/mL against Candida albicans. The quantum parameters that relate to the bioavailability of the compounds were computed, followed by docking with different bacterial and fungal targets like sortase A, dihydrofolate reductase, thymidylate kinase, gyrase B, sterol 14-alpha demethylase. The experimental and computational results are in good agreement.

Oxadiazole: A highly versatile scaffold in drug discovery.

As a pharmacologically important heterocycle, oxadiazole paved the way to combat the problem associated with the confluence of many commercially available drugs with different pharmacological profiles. The present review focuses on the potential applications of five-membered heterocyclic oxadiazole derivatives, especially 1,2,4-oxadiazole, 1,2,5-oxadiazole, and 1,3,4-oxadiazole, as therapeutic agents. Designing new hybrid molecules containing the oxadiazole moiety is a better solution for the development of new drug molecules. The designed molecules may accumulate a biological profile better than those of the drugs currently available on the market. The present review will guide the way for researchers in the field of medicinal chemistry to design new biologically active molecules based on the oxadiazole nucleus. Antitubercular, antimalarial, anti-inflammatory, anti-HIV, antibacterial, and anticancer activities of various oxadiazoles have been reviewed extensively here.

Synthesis, molecular docking, DFT study, and in vitro antimicrobial activity of some 4-(biphenyl-4-yl)-1,4-dihydropyridine and 4-(biphenyl-4-yl)pyridine derivatives.

The evolution of microbial resistance necessitates the development of new antimicrobial drugs that are more effective than those currently on the market. To address this problem, we have prepared a series of novel 4-(biphenyl-4-yl)-1,4-dihydropyridine and 4-(biphenyl-4-yl)pyridine derivatives via Hantzsch reaction using nine different compounds containing active methylene group. IR, NMR, and mass spectra were used to determine the structures. Using ampicillin and griseofulvin as standards, the titled compounds were investigated for their antibacterial activity against different bacteria and fungi. Compounds 1f, 1g, 2f, and 2g have the best antibacterial activity against Gram-negative bacteria (minimum inhibitory concentration = 50 µg/ml), while 1f, 1h, 2g, and 2h have high antifungal activity against Candida albicans (minimum inhibitory concentration = 100 µg/ml). To gain a better understanding of the binding process and affinity for the bacterial Staphylococcus epidermidis protein, researchers used molecular docking and molecular mechanics, as well as the generalized Born model and solvent accessibility-based binding free energy. The active compounds 1g, 1h, and 2f have good docking scores of -5.575, -5.949, and -5.234, respectively, whereas compound 2c has the greatest docking score (-6.23). The HOMO-LUMO energy gap and molecular electrostatic potential were used to evaluate the reactivity of promising compounds, which were then associated with antibacterial efficacy.

Synthesis, Antifungal Ergosterol Inhibition, Antibiofilm Activities, and Molecular Docking on ß-Tubulin and Sterol 14-Alpha Demethylase along with DFT-Based Quantum Mechanical Calculation of Pyrazole Containing Fused Pyridine-Pyrimidine Derivatives.

Multidrug-resistant fungal infections have become much more common in recent years, especially in immune-compromised patients. Therefore, researchers and pharmaceutical professionals have focused on the development of novel antifungal agents that can tackle the problem of resistance. In continuation to this, a novel series of pyrazole-bearing pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives (4a-4o) have been developed. These compounds have been screened against Candida albicans, Aspergillus niger, and Aspergillus clavatus. The synthesized compounds were characterized by well-known spectroscopic techniques, i.e., IR, 1H NMR, 13C NMR, and mass spectrometry. In vitro antifungal results revealed that compound 4n showed activity against C. albicans having MIC value of 200 µg/mL. To know the plausible mode of action, the active derivatives were screened for anti-biofilm and ergosterol biosynthesis inhibition activities. The compounds 4h, 4j, 4k, and 4n showed greater ergosterol biosynthesis inhibition than the control DMSO. To comprehend how molecules interact with the receptor, studies of molecular docking of 4k and 4n have been performed on the homology-modeled protein of ß-tubulin. The molecular docking revealed that the active compounds 4h, 4j, 4k, 4l, and 4n interacting with the active site amino acid of sterol 14-alpha demethylase (PDB ID: 5v5z) indicate one of the possible modes of action of ergosterol inhibition activity. The synthesized compounds 4c, 4e, 4h, 4i, 4j, 4k, 4l, and 4n inhibited biofilm formation and possessed the potential for anti-biofilm activity. DFT-based quantum mechanical calculations were carried out to optimize, predict, and compare the vibration modes of the molecule 4a.

Conventional and Microwave-Assisted Synthesis, Antitubercular Activity, and Molecular Docking Studies of Pyrazole and Oxadiazole Hybrids.

Microwave-assisted organic reaction enhancement (MORE) has become more important in synthetic organic chemistry for efficient resource utilization. In this study, we synthesized bioactive compounds using both traditional and microwave methods. Microwave-assisted synthesis takes less time and produces higher yields and quality than conventional approaches. We reported the synthesis of N'-(1-(2-(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazol-3(2H)-yl)ethylidene) substituted hydrazides (4a-t). We also tested them against two strains: M. tuberculosis H37Ra and M. bovis BCG. Against M. tuberculosis H37Ra, the compounds 4e, 4h, 4k, 4p, and 4s were the most effective. Compounds 4f, 4g, and 4s showed significant activity against M. bovis BCG. The structures of newly synthesized molecules were determined using spectral methods. Furthermore, molecular docking investigations into the active site of mycobacterial InhA yielded well-clustered solutions for these compounds' binding modalities producing a binding affinity in the range of -10.366 to -8.037. Theoretical results were in good accord with the observed experimental values. The docking score of compound 4e was -10.366, and the Glide energy was -66.459 kcal/mol.