Novel 4,6-Disubstituted s-Triazin-2-yl Amino Acid Derivatives as Promising Antifungal Agents

Rakia Abd Alhameed; Zainab Almarhoon; Essam N Sholkamy; Salman Ali Khan; Zaheer Ul-Haq; Anamika Sharma; Beatriz G de la Torre; Fernando Albericio; Ayman El-Faham

doi:10.3390/jof6040237

Novel 4,6-Disubstituted s-Triazin-2-yl Amino Acid Derivatives as Promising Antifungal Agents

J Fungi (Basel). 2020 Oct 21;6(4):237. doi: 10.3390/jof6040237.

Authors

Rakia Abd Alhameed¹, Zainab Almarhoon¹, Essam N Sholkamy², Salman Ali Khan³, Zaheer Ul-Haq³, Anamika Sharma^{4

5}, Beatriz G de la Torre^{4

5}, Fernando Albericio^{1

5

6

7}, Ayman El-Faham^{1

8}

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
² Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
³ Dr. Panjwani Center for Molecular medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
⁴ KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa.
⁵ Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South Africa.
⁶ CIBER-BBN (Networking Centre on Bioengineering, Biomaterials and Nanomedicine) and Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain.
⁷ Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), 08034 Barcelona, Spain.
⁸ Chemistry Department, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia 12321, Alexandria, Egypt.

Abstract

A novel series of 4,6-disubstituted s-triazin-2-yl amino acid derivatives was prepared and characterized. Most of them showed antifungal activity against Candida albicans compared to clotrimazole (standard drug). Compounds bearing aniline derivatives, piperidine and glycine on the triazine core showed the highest inhibition zones at concentrations of 50, 100, 200, and 300 μg per disc. In addition, docking studies revealed that all the compounds accommodated well in the active site residues of N-myristoltransferase (NMT) and exhibited complementarity, which explains the observed antifungal activity. Interestingly, none of these compounds showed antibacterial activity.

Keywords: 2,4,6-trichlorotriazine; Candida albicans; N-myristoltransferase; TCT; antifungal; triazine amino acid.

Abstract

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