TY - JOUR

T1 - Modifications of isoalantolactone leading to effective anti-bacterial and anti-viral compounds

AU - Patrushev, Sergey S.

AU - Burova, Lyubov G.

AU - Shtro, Anna A.

AU - Rybalova, Tatyana V.

AU - Baev, Dmitry S.

AU - Shirokikh, Il’Ya V.

AU - Evstropov, Alexander N.

AU - Shults, Elvira E.

N1 - Funding Information: This work was supported by the Russian Science Foundation (project № 18-13-00361). Publisher Copyright: © 2021 Bentham Science Publishers.

PY - 2021/7

Y1 - 2021/7

N2 - Background: Natural sesquiterpene lactones are an important class of heterocyclic compounds in drug discovery since they possess a wide range of biological properties, including antibacterial activity. Objective: The objective of this study was to synthesize isoalantolactone derivatives with a furo[2,3-d] pyrimidin-2-оne moiety, and to evaluate their antibacterial and antiviral activity. Methods: The Sonogashira cross-coupling and subsequent Ag-catalyzed cyclization reactions were used forthe synthesis. The antibacterial activity and the ability to inhibit biofilms formation on E. coli, S. aureus, A. viscosus, P. aeruginosa, and E. faecalis bacterial strains were evaluated in this study. A study of the molecular interactions of new compounds with the multiple virulence factor regulators was performed using docking simulations. The anti-viral activity against influenza A virus and human orthopneumovirus H-2А was also studied. Results: The in vitro anti-bacterial activity for compound 4 (MIC = 58.33 ± 4.41 μg/mL) concerning E. coli and compound 5 (MIC = 96.5 ± 3.25 μg/mL) against A. viscosus and the inhibition of biofilm formation for compounds 2, 4, and 5 on E. coli, S. aureus, P. aeruginosa, and E. faecalis bacterial strains, have been of interest for the search of improved anti-microbial agents. Compound 3 possessed antiviral activity against human orthopneumovirus H-2А with SI >33. The activity of the new type of hybrid compounds is dependent on the substituent in the 6th position of the furo[2,3-d] pyrimidin-2-one fragment. Conclusion: The decoration of isoalantolactone with a furo[2,3-d]pyrimidin-2-one fragment led to the development of antiviral and antimicrobial agents. Due to the antimicrobial activity, pyridine-4-yl substituted isoalantolactone-furopyrimidinone hybrid is considered as a candidate compound to participate in further research.

AB - Background: Natural sesquiterpene lactones are an important class of heterocyclic compounds in drug discovery since they possess a wide range of biological properties, including antibacterial activity. Objective: The objective of this study was to synthesize isoalantolactone derivatives with a furo[2,3-d] pyrimidin-2-оne moiety, and to evaluate their antibacterial and antiviral activity. Methods: The Sonogashira cross-coupling and subsequent Ag-catalyzed cyclization reactions were used forthe synthesis. The antibacterial activity and the ability to inhibit biofilms formation on E. coli, S. aureus, A. viscosus, P. aeruginosa, and E. faecalis bacterial strains were evaluated in this study. A study of the molecular interactions of new compounds with the multiple virulence factor regulators was performed using docking simulations. The anti-viral activity against influenza A virus and human orthopneumovirus H-2А was also studied. Results: The in vitro anti-bacterial activity for compound 4 (MIC = 58.33 ± 4.41 μg/mL) concerning E. coli and compound 5 (MIC = 96.5 ± 3.25 μg/mL) against A. viscosus and the inhibition of biofilm formation for compounds 2, 4, and 5 on E. coli, S. aureus, P. aeruginosa, and E. faecalis bacterial strains, have been of interest for the search of improved anti-microbial agents. Compound 3 possessed antiviral activity against human orthopneumovirus H-2А with SI >33. The activity of the new type of hybrid compounds is dependent on the substituent in the 6th position of the furo[2,3-d] pyrimidin-2-one fragment. Conclusion: The decoration of isoalantolactone with a furo[2,3-d]pyrimidin-2-one fragment led to the development of antiviral and antimicrobial agents. Due to the antimicrobial activity, pyridine-4-yl substituted isoalantolactone-furopyrimidinone hybrid is considered as a candidate compound to participate in further research.

KW - Antibacterial activity

KW - Antiviral activity

KW - Cross-coupling reaction

KW - Cyclization

KW - Natural products

KW - Pyrimidine

KW - Sesquiterpene lactone

UR - http://www.scopus.com/inward/record.url?scp=85114129955&partnerID=8YFLogxK

U2 - 10.2174/1570180817999201211193151

DO - 10.2174/1570180817999201211193151

M3 - Article

AN - SCOPUS:85114129955

VL - 18

SP - 686

EP - 700

JO - Letters in Drug Design and Discovery

JF - Letters in Drug Design and Discovery

SN - 1570-1808

IS - 7

ER -