Molecular docking aided machine learning for the identification of potential VEGFR inhibitors against renal cell carcinoma.

Renal cell carcinoma is a highly vascular tumor associated with vascular endothelial growth factor (VEGF) expression. The Vascular Endothelial Growth Factor -2 (VEGF-2) and its receptor was identified as a potential anti-cancer target, and it plays a crucial role in physiology as well as pathology. Inhibition of angiogenesis via blocking the signaling pathway is considered an attractive target. In the present study, 150 FDA-approved drugs have been screened using the concept of drug repurposing against VEGFR-2 by employing the molecular docking, molecular dynamics, grouping data with Machine Learning algorithms, and density functional theory (DFT) approaches. The identified compounds such as Pazopanib, Atogepant, Drosperinone, Revefenacin and Zanubrutinib shown the binding energy - 7.0 to - 9.5 kcal/mol against VEGF receptor in the molecular docking studies and have been observed as stable in the molecular dynamic simulations performed for the period of 500 ns. The MM/GBSA analysis shows that the value ranging from - 44.816 to - 82.582 kcal/mol. Harnessing the machine learning approaches revealed that clustering with K = 10 exhibits the relevance through high binding energy and satisfactory logP values, setting them apart from compounds in distinct clusters. Therefore, the identified compounds are found to be potential to inhibit the VEGFR-2 and the present study will be a benchmark to validate the compounds experimentally.

Design, synthesis and in silico molecular docking evaluation of novel 1,2,3-triazole derivatives as potent antimicrobial agents.

Chalcone and triazole scaffolds have demonstrated a crucial role in the advancement of science and technology. Due to their significance, research has proceeded on the design and development of novel benzooxepine connected to 1,2,3-triazolyl chalcone structures. The new chalcone derivatives produced by benzooxepine triazole methyl ketone 2 and different aromatic carbonyl compounds 3 are discussed in this paper. All prepared compounds have well-established structures to a variety of spectral approaches, including mass analysis, 1H NMR, 13C NMR, and IR. Among the tested compounds, hybrids 4c, 4d, 4i, and 4k exhibited exceptional antibacterial susceptibilities with MIC range of 3.59-10.30 µM against the tested S. aureus strain. Compounds 4c, 4d displayed superior antifungal activity against F. oxysporum with MIC 3.25, 4.89 µM, when compared to fluconazole (MIC = 3.83 µM) respectively. On the other hand, analogues 4d, 4f, and 4k demonstrated equivalent antitubercular action against H37Rv strain with MIC range of 2.16-4.90 µM. The capacity of ligand 4f to form a stable compound on the active site of CYP51 from M. tuberculosis (1EA1) was confirmed by docking studies using amino acids Leu321(A), Pro77(A), Phe83(A), Lys74(A), Tyr76(A), Ala73(A), Arg96(A), Thr80(A), Met79(A), His259(A), and Gln72(A). Additionally, the chalcone‒1,2,3‒triazole hybrids ADME (absorption, distribution, metabolism, and excretion), characteristics of molecules, estimations of toxicity, and bioactivity parameters were assessed.

A Highly Selective Schiff Base Based Chemodosimeter for the Detection of Perfluorooctanoic Acid by Optical Biosensor.

A simple imine derivative based sensor (IDP) has been synthesized and characterized by 1 H NMR, 13 C NMR and mass spectral techniques. IDP is more capable of detecting perfluorooctanoic acid (PFOA) in a selective and sensitive manner. The PFOA as a biomarker interacts with IDP and shows "TURN-ON" response by colorimetric and fluorimetric method. Under optimized experimental observations, the selective determination of PFOA using IDP among other competitors as biomolecules has been noticed. The detection limit is 0.31 × 10- 8 mol/L. The practical applications of the IDP is effectively evaluated in human biofluids and water samples.

Green synthesis of naphthyl derivative as an optical sensor for the detection of l-carnitine in food samples.

An economical and green approach to the synthesis of naphthyl derivative for detection of l-carnitine (3-hydroxy-4-N-trimethyl-aminobutyrate) is practically important. We developed a naphthyl derivative as a probe showing 'turn-on' response towards l-carnitine selectively at pH 7.2 through ICT mechanism with a good limit of detection (LOD) of 0.126 µM. Using Job's plot for determining the binding stoichiometry, it was found that probe could form a more stable complex (1:1) with carnitine. The binding constant (K) between probe and carnitine was calculated as 8 × 107  M-1 using the Benesi-Hildebrand plot. The binding interaction of the probe with l-carnitine was confirmed by nuclear magnetic resonance titrations, Fourier-transform infrared spectroscopy, photo physical studies and density functional theory calculations. Meanwhile, the probe can be used to quantitatively detect carnitine in food samples.

Highly Sensitive and Selective Detection of Melatonin in Biofluids by Antipyrine Based Fluorophore.

A simple fluorescent based organic fluorophore was synthesized and it shows significant fluorescent intensity with melatonin (MLN). Hence, it was applicable to the detection of MLN by colorimetric and fluorimetric techniques at neutral pH. Under optimized experimental condition, the synthesized organic fluorophore detects MLN selectively in the presence of other interfering biomolecules through ICT mechanism. The melatonin sensing mechanism is supported by DFT and 1H-NMR titration. Based on the findings, this method can be applied to design a simple clinical diagnostic tool for MLN.

Computational investigation on microsolvation of the osmolyte glycine betaine [GB (H(2)O)(1-7)].

The preferential interactions of glycine betaine (GB) with solvent components and the effect of solvent on its stability have been examined. In particular, the microsolvation of organic osmolyte and widely important osmoprotectant in nature as glycine betaine has been reported by using M06 method. A number of configurations (b(X) (a-z)) of the clusters for one to seven water molecules (× = 1-7) have been considered for the microsolvation. Structures of stable conformers are obtained and denoted as b1a, b2a, b3a, b4a, b5a, b6a and b7a. It is observed from the interaction energy difference (∆E) that only seven water molecules can be accommodated in the first solvation shell to stabilize GB. It is also observed that the calculated relative energy using M06 is in close agreement with calculations at the MP2 level of theory.