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Rational Design of New Monoterpene-Containing Azoles and Their Antifungal Activity Full article

Journal Antibiotics
ISSN: 2079-6382
Output data Year: 2023, Volume: 12, Number: 5, Pages: 818 Pages count : 1 DOI: 10.3390/antibiotics12050818
Tags triazole antifungals; monoterpenoids; hybrids; clinical isolates; CYP51; Candida spp.
Authors Li-Zhulanov Nikolai S. 1 , Zaikova Nadezhda P. 1 , Sari Suat 2 , Gülmez Dolunay 3 , Sabuncuoğlu Suna 4 , Ozadali-Sari Keriman 2 , Arikan-Akdagli Sevtap 3 , Nefedov Andrey A. 1 , Rybalova Tatyana V. 1 , Volcho Konstantin P. 1 , Salakhutdinov Nariman F. 1
Affiliations
1 N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentiev Ave., 9, 630090 Novosibirsk, Russia
2 Department of Pharmaceutical Chemistry, Hacettepe University Faculty of Pharmacy, Sihhiye, Ankara 06100, Turkey
3 Department of Medical Microbiology, Hacettepe University Faculty of Medicine, Sihhiye, Ankara 06100, Turkey
4 Department of Pharmaceutical Toxicology, Hacettepe University Faculty of Pharmacy, Sihhiye, Ankara 06100, Turkey

Funding (1)

1 Российский Научный Фонд 22-73-00046

Abstract: Azole antifungals, including fluconazole, have long been the first-line antifungal agents in the fight against fungal infections. The emergence of drug-resistant strains and the associated increase in mortality from systemic mycoses has prompted the development of new agents based on azoles. We reported a synthesis of novel monoterpene-containing azoles with high antifungal activity and low cytotoxicity. These hybrids demonstrated broad-spectrum activity against all tested fungal strains, with excellent minimum inhibitory concentration (MIC) values against both fluconazole-susceptible and fluconazole-resistant strains of Candida spp. Compounds 10a and 10c with cuminyl and pinenyl fragments demonstrated up to 100 times lower MICs than fluconazole against clinical isolates. The results indicated that the monoterpene-containing azoles had much lower MICs against fluconazole-resistant clinical isolates of Candida parapsilosis than their phenyl-containing counterpart. In addition, the compounds did not exhibit cytotoxicity at active concentrations in the MTT assay, indicating potential for further development as antifungal agents.
Cite: Li-Zhulanov N.S. , Zaikova N.P. , Sari S. , Gülmez D. , Sabuncuoğlu S. , Ozadali-Sari K. , Arikan-Akdagli S. , Nefedov A.A. , Rybalova T.V. , Volcho K.P. , Salakhutdinov N.F.
Rational Design of New Monoterpene-Containing Azoles and Their Antifungal Activity
Antibiotics. 2023. V.12. N5. P.818. DOI: 10.3390/antibiotics12050818 WOS РИНЦ
Dates:
Submitted: Apr 10, 2023
Accepted: Apr 25, 2023
Published online: Apr 27, 2023
Identifiers:
Web of science WOS:000994782500001
Elibrary 61323887
OpenAlex W4367297954
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