Design, Synthesis of Some Innovative Indolo[3,2-c]Isoquinoline-5-One Analogs and Associated Bioactivities, Pharmacophore, Molecular Docking, MEP, and Conceptual DFT Studies

A series of novel triazolothiadiazolethione and triazolothiadiazine appended indolo[3,2-c]isoquinoline-5-one were designed, synthesized, and validated by IR, 1 H, 13 C NMR, and mass spectroscopy strategies. All compounds are determined by their DFT investigations with B3LYP/def2-TZVP basis set level...

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Published in:Polycyclic aromatic compounds 2023-10, Vol.43 (9), p.8408-8425
Main Authors: Verma, Vaijinath A., Shinde, Venkat M., Saundane, Anand R., Meti, Rajkumar S., Vennapu, Dushyanth R.
Format: Article
Language:English
Subjects:
Adiabatic
Anticancer properties
Antimicrobial activity
Bacteria
Binding sites
Dipole moments
Drug development
electron affinity
Fungicides
Gram-negative bacteria
Gram-positive bacteria
Indoloisoquinoline
Ionization
ionization potential
Ionization potentials
Mass spectroscopy
Molecular docking
Molecular orbitals
NMR
Nuclear magnetic resonance
Parameters
pharmacophore
Softness
topoisomerases
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Summary:A series of novel triazolothiadiazolethione and triazolothiadiazine appended indolo[3,2-c]isoquinoline-5-one were designed, synthesized, and validated by IR, 1 H, 13 C NMR, and mass spectroscopy strategies. All compounds are determined by their DFT investigations with B3LYP/def2-TZVP basis set level, ionization potentials, and electron affinities at vertical (IPv and EAv) and adiabatic parameters (IP A and EA A ). Compound 3a has demonstrated the greatest values for these parameters. The compounds' HOMO-LUMO (FMOs) and MEP maps were performed. The optimized structure of the compounds was estimated in global hardness, softness, global electrophilicity, and dipole moment. To find new drug candidates, different in vitro biological activities were implemented employing antimicrobial activity: Gram-negative bacteria were significantly suppressed by compound 4a, whereas gram-positive bacteria were strongly inhibited by compounds 3c and 3a has significant antifungal and anticancer effects. Compound 4b is profoundly antioxidant with IC 50 value of 8.74 ± 1.93 µg/mL and MIC value of 0.25 µg/mL for antituberculosis properties. Thereafter, all of the compounds were subjected to e-pharmacophore approach to molecular docking studies. Compound 4a exhibited the best docking score (−8.458 kcal/mol) and docking interactions with active binding sites of 1TL8 receptor.
ISSN:1040-6638
1563-5333
DOI:10.1080/10406638.2022.2149573