1,2,3-Triazole-quinazolin-4(3H)-one conjugates

evolution of ergosterol inhibitor as anticandidal agent

Mir Mohammad Masood, Mohammad Irfan, Parvez Khan, Mohamed F. Alajmi, Afzal Hussain, Jered C Garrison, Md Tabish Rehman, Mohammad Abid

Research output: Contribution to journalArticle

Abstract

The present study describes the synthesis of 1,2,3-triazole-quinazolinone conjugates (5a-q) from ethyl 4-oxo-3-(prop-2-ynyl)-3,4-dihydroquinazoline-2-carboxylate and phenyl azide/substituted phenyl azides employing Cu(i) catalysed Huisgen 1,3-dipolar cycloaddition. The corresponding acids (6a-q) were obtained by hydrolysis of esters (5a-q) to study the effect of these functionalities on the biological activity. All synthesized compounds were screened for in vitro anticandidal evaluation against Candia albicans, Candida glabrata and Candida tropicalis strains. The results indicated that compound 5n showed potent anticandidal activity with IC50 in the range of 8.4 to 14.6 μg mL−1. Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed the non-toxic nature of the selected compounds. Growth kinetic study with compound 5n showed its fungicidal nature as no significant growth of Candida cells was observed even after 24 h. Cellular ergosterol content was determined in the presence of different concentrations of 5n to measure the activity of lanosterol 14α-demethylase indirectly. The results showed significant disruption of the ergosterol biosynthetic pathway through inhibition of lanosterol 14α-demethylase activity supported by docking studies (PDB: 5v5z). Overall, this study demonstrates the anticandidal potential of 5n which can serve as the lead for further structural optimization and SAR studies.

Original languageEnglish (US)
Pages (from-to)39611-39625
Number of pages15
JournalRSC Advances
Volume8
Issue number69
DOIs
StatePublished - Jan 1 2018

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Ergosterol
Triazoles
Candida
Lanosterol
Azides
Quinazolinones
Cycloaddition
Structural optimization
Growth kinetics
Cytotoxicity
Bioactivity
Hydrolysis
Assays
Esters
Blood
Lead
Cells
Acids

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

1,2,3-Triazole-quinazolin-4(3H)-one conjugates : evolution of ergosterol inhibitor as anticandidal agent. / Masood, Mir Mohammad; Irfan, Mohammad; Khan, Parvez; Alajmi, Mohamed F.; Hussain, Afzal; Garrison, Jered C; Rehman, Md Tabish; Abid, Mohammad.

In: RSC Advances, Vol. 8, No. 69, 01.01.2018, p. 39611-39625.

Research output: Contribution to journalArticle

Masood, MM, Irfan, M, Khan, P, Alajmi, MF, Hussain, A, Garrison, JC, Rehman, MT & Abid, M 2018, '1,2,3-Triazole-quinazolin-4(3H)-one conjugates: evolution of ergosterol inhibitor as anticandidal agent', RSC Advances, vol. 8, no. 69, pp. 39611-39625. https://doi.org/10.1039/c8ra08426b
Masood, Mir Mohammad ; Irfan, Mohammad ; Khan, Parvez ; Alajmi, Mohamed F. ; Hussain, Afzal ; Garrison, Jered C ; Rehman, Md Tabish ; Abid, Mohammad. / 1,2,3-Triazole-quinazolin-4(3H)-one conjugates : evolution of ergosterol inhibitor as anticandidal agent. In: RSC Advances. 2018 ; Vol. 8, No. 69. pp. 39611-39625.
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