Abstract
A series of novel 5-(3,5-disubstituted-1H-indol-2-yl)-2,3-dimethyl-1-phenyl-2,6-dihydro-1H-pyrazolo[4,3-e][1,2,4]triazines (3a-l) were synthesized in single step from 3,5-disubstituted indole-2-carbohydrazide and 4-aminoantipyrine under acidic conditions with excellent yields. The various spectroscopic methods were used to prove the formation of all these products. The compounds 3a, 3b, 3e, 3f, 3i and 3j exhibited excellent antibacterial and antifungal activities with an MIC value of 3.125 µg/ml against the tested pathogens and anti-tuberculosis inhibitory potential against M. tuberculosis which is equivalent to standard drug. The antidiabetic activity of the compounds 3a and 3b showed the maximum potential as glucosidase inhibitors with IC50 = 47.21 μg/ml and IC50 = 48.36 μg/ml, respectively. The physicochemical characteristics like ADMET, drug-likeness and bioactivity scores for these molecules were also disclosed. To comprehend the electronic behavior of compound 3a, density functional theory estimations at the DFT/B3LYP level via 6-31G++ (d, p) have been carried out to replicate the structure and geometry. The first-order hyperpolarizability calculation was used to calculate the nonlinear visual feature of compound 3a. The charge transfer interface among the structure is elucidated by the estimated HOMO–LUMO analysis. Further, molecular docking studies were carried out for synthesized compounds with human maltase-glucoamylase (PDB: 2QMJ).
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Acknowledgements
The authors are grateful to The Directors of IISc, Bengaluru, SAIF Punjab University, and CDRI, Lucknow, for spectral data. For biological activities, the authors are grateful to The Director, Skanda Life Sciences Pvt. Ltd., Bengaluru-560 091. Thanks are due to The Principal, Vijaya College, Bengaluru-560 004 and The Principal, Guru Nanak First Grade College, Bidar—585 403, for providing laboratory facilities to the authors.
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Basavarajaiah, S.M., Nagesh, G.Y., Javeed, M. et al. Synthesis, spectral analysis, DFT calculations, biological potential and molecular docking studies of indole appended pyrazolo-triazine. Mol Divers 27, 679–693 (2023). https://doi.org/10.1007/s11030-022-10448-y
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DOI: https://doi.org/10.1007/s11030-022-10448-y