A Series of Novel Integrastatins Analogues: In silico Study of Physicochemical and Bioactivity Parameters
Rakhimzhanova A.S. Muzaparov R.A. Pustolaikina I.A. Kurmanova A.F. Nikolskiy S.N. Kapishnikova D.D. Stalinskaya A.L. Kulakov I.V.
2024E.A. Buketov Karaganda University Publish house
Eurasian Journal of Chemistry
2024#116Issue 444 - 60 pp.
Integrastatins are naturally occurring heterotetracyclic compounds with a broad spectrum of biological activi-ty. A number of new structural analogues of integrastatins 2a-u have been synthesized using a novel one-step method [1], but a systematic theoretical study of their structural features and biological activity has not been realized. This study aimed to in silico investigate physicochemical and bioactivity properties for a series of 21 new synthetic analogues of natural integrastatins. Global chemical reactivity descriptors was assessed using DFT B3LYP 6-311++G(d, p) CPCM (solvent — water) calculations. High ionization potential IP in the range from 5.9 to 7.1 eV and electron affinity EA at the level of 2.1 to 3.2 eV were shown, which together with a sufficiently large energy gap DEgap from 3.8 to 4.6 eV indicates the hard nature of the compounds 2a-u. Antiviral activity and inhibitory potential as CYP2C19 inducers were identified using the PASSOnline resource. According to the results of molecular docking studies Human immunodeficiency virus HIV-1 reverse tran-scriptase protein (PDB ID: 3V81) and protein of the RNA-dependent RNA polymerase of the SARS-CoV-2 (PDB ID: 7AAP) can serve as a likely biological target for the compounds 2a-u. Potentially high oral efficacy and a promising safety profile for the therapeutic use were showed using ADMETlab 3.0 online portal. Fur-ther experimental in vitro and in vivo studies of the pharmaceutical potential of compounds 2a-u is need for more accurate evaluation the assumptions made on the basis of in silico approach.
ADMET , antiviral activity , B3LYP , biological activity , computational study , DFT , global chemical reactivity descriptors , HIV-1 , in silico , integrastatins , molecular docking , quantum chemical calculations , SARS-CoV-2
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Department of Physical and Analytical Chemistry, Karaganda Buketov University, Universitetskaya street, 28, Karaganda, 100024, Kazakhstan
Institute of Chemistry, Saint Petersburg State University, Universitetskii prospect, 26, Saint Petersburg, 198504, Russian Federation
School of Natural Sciences, University of Tyumen, 15a Perekopskaya St., Tyumen, 625003, Russian Federation
Higher School of Natural Science, University of Tyumen, 15a Perekopskaya St, Tyumen, 625003, Russian Federation
Department of Physical and Analytical Chemistry
Institute of Chemistry
School of Natural Sciences
Higher School of Natural Science
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