In Silico Evaluation of the Antibacterial and Antiviral Potential of Nusbiarylin Derivatives

Ognjen Milić; Nikola Nedeljković; Miloš Nikolić

doi:10.5937/arhfarm76-67266

Ognjen Milić Univerzitet u Beogradu – Farmaceutski fakultet, Katedra za farmaceutsku tehnologiju i kozmetologiju, Beograd, Srbija
Nikola Nedeljković Univerzitet u Kragujevcu – Fakultet medicinskih nauka, Odsek za farmaciju, Kragujevac, Srbija
Miloš Nikolić Univerzitet u Kragujevcu – Fakultet medicinskih nauka, Odsek za farmaciju, Kragujevac, Srbija

DOI: https://doi.org/10.5937/arhfarm76-67266

Ključne reči: molekulski doking, derivati nusbiarilina, analiza sličnosti sa lekom, RNK polimeraza, HCV RNAP, dualni inhibitori

Sažetak

Antimikrobna rezistencija i hronične virusne infekcije predstavljaju značajne izazove u savremenoj medicini. U ovoj in silico studiji ispitivan je dualni inhibitorni potencijal 16 dizajniranih derivata nusbiarilina prema dva klinički relevantna enzimska cilja: RNK polimerazi bakterije Escherichia coli (E. coli) (RNAP) i RNK-zavisnoj RNK polimerazi virusa hepatitisa C (HCV RNAP). Semifleksibilno molekulsko doking ispitivanje sprovedeno je korišćenjem softvera AutoDock Vina. Šest jedinjenja – 5, 6, 7, 8, 15 i 16 – pokazala su najpovoljniji dualni inhibitorni potencijal, formirajući ključne vodonične veze sa Ser642 E. coli RNAP i sa Tyr477 i Arg422 HCV RNAP, uz značajne hidrofobne interakcije. Prisustvo cijano ili nitrozo grupa kao akceptora vodoničnih veza, kao i sulfonil ili sulfoksidnih grupa koje doprinose π-S interakcijama, identifikovano je kao ključna strukturna determinanta afiniteta vezivanja za oba ciljna mesta. Ovi rezultati podržavaju dalje eksperimentalno ispitivanje derivata nusbiarilina kao potencijalnih dualnih antibakterijskih i antivirusnih agenasa.

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In silico ispitivanje antibakterijskog i antivirusnog potencijala derivata nusbiarilina

Sažetak

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