Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Synthesis, antimicrobial activities and GAPDH docking of novel 1, 2, 3-triazole derivatives

Abdulsalam AM Alkhaldi¹, Mohamed A Abdelgawad^2,3 , Bahaa GM Youssif^2,4, Ahmed O El-Gendy⁵, Harry P De Koning⁶

¹Biology Department, College of Science, Jouf University, Sakaka, Aljouf 2014, Saudi Arabia; ²Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Aljouf 2014, Saudi Arabia; ³Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; ⁴Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt; ⁵Department of Microbiology & Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; ⁶Institute of Infection, Immunity and In@258;ammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, United Kingdom.

For correspondence:- Mohamed Abdelgawad Email: mohamedabdelwahab976@yahoo.com Tel:+20238482600

Accepted: 24 April 2019 Published: 31 May 2019

Citation: Alkhaldi AA, Abdelgawad MA, Youssif BG, El-Gendy AO, De Koning HP. Synthesis, antimicrobial activities and GAPDH docking of novel 1, 2, 3-triazole derivatives. Trop J Pharm Res 2019; 18(5):1101-1108 doi: 10.4314/tjpr.v18i5.27

© 2019 The authors.
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Abstract

Purpose: To synthesize new triazole derivatives in order to overcome the problem of side effects of antimicrobial agents and microbial resistance, while broadening the spectrum of antimicrobial activity.

Methods: The starting triazole, compound 1, was prepared through click chemistry and reacted with chloroacetyl chloride to yield compound II. Triazole 1 was reacted with acids and aldehydes to produce oxadiazole (III) and azomethine (IV) which cyclized in acetic anhydride to give a new acetylated oxadiazole (V). Minimum inhibitory concentration (MIC) and resorufin assays were used for antibacterial and anti-parasitic screening, respectively. Compounds II and IVb were subjected to molecular docking studies using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) Molecular Operating Environment (MOE) program.

Results: Novel oxazole-triazole derivative (III) showed high activity against Pseudomonas aeruginosa and moderate activity against Staphylococcus epidermidis, whereas compound IVc showed moderate activity against Staphylococcus epidermidis. Chloro-acetyl-triazole II and 2-hydroxyphenyl-triazole Schiff base (Ivb) showed pronounced activity against the kinetoplastid parasites, Leishmania major, Leishmania mexicana and Trypanosoma brucei.

Conclusion: The new synthesized triazoles represent a new antimicrobial scaffold and identifies potential new lead compounds for follow-up and for further mechanistic studies.

Keywords: Antimicrobial, Triazole, Trypanosoma, Leishmania, Kinetoplastid