Back to Journals » Drug Design, Development and Therapy » Volume 15

Nα-1, 3-Benzenedicarbonyl-Bis-(Amino Acid) and Dipeptide Candidates: Synthesis, Cytotoxic, Antimicrobial and Molecular Docking Investigation

Authors Naglah AM, Moustafa GO, Elhenawy AA, Mounier MM, El-Sayed H, Al-Omar MA, Almehizia AA, Bhat MA

Received 14 August 2020

Accepted for publication 23 January 2021

Published 25 March 2021 Volume 2021:15 Pages 1315—1332


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos

Ahmed M Naglah,1,2 Gaber O Moustafa,2 Ahmed A Elhenawy,3,4 Marwa M Mounier,5 Heba El-Sayed,6 Mohamed A Al-Omar,1 Abdulrahman A Almehizia,1,7 Mashooq A Bhat7

1Department of Pharmaceutical Chemistry, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia; 2Peptide Chemistry Department, Chemical Industries Research Division, National Research Centre, Cairo, Egypt; 3Chemistry Department, Faculty of Science, Al-Azhar University (Boys’Branch), Cairo, Egypt; 4Chemistry Department, Faculty of Science, Albaha University, Al Baha, Saudi Arabia; 5Pharmacognosy Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Giza, Egypt; 6Botany and Microbiology Department, Faculty of Science, Helwan University, Helwan, Egypt; 7Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia

Correspondence: Gaber O Moustafa; Ahmed Elhenawy Tel +201003123355
; +966599044526
Email [email protected]; [email protected]

Purpose: The objective of our work was to prepare a potent and safe antimicrobial and anticancer agents, through synthesis of several peptides and examine their biological activities, namely as, cytotoxically potent and antimicrobial and antifungal agents.
Introduction: Multidrug-resistant microbial strains have arisen against all antibiotics in clinical use. Infections caused by these bacteria threaten global public health and are associated with high mortality rates.
Methods: The main backbone structure for the novel synthesized linear peptide is Nα-1, 3-benzenedicarbonyl-bis-(Amino acids)-X, ( 3– 11). A computational docking study against DNA gyrase was performed to formulate a mode of action of the small compounds as antimicrobial agents.
Results: The peptide-bearing methionine-ester ( 4) exhibited potent antimicrobial activity compared to the other synthesized compounds, while, peptide ( 8), which had methionine-hydrazide fragment was the most potent as antifungal agent against Aspergillus niger with 100% inhibition percent. Compounds ( 6 and 7) showed the highest potency against breast human tumor cell line “MCF-7” with 95.1% and 79.8% of cell inhibition, respectively. The nine compounds possessed weak to moderate antiproliferative effect over colon tumor cell line. The docking results suggest good fitting through different hydrogen bond interactions with the protein residues. In silico ADMET study also evaluated and suggested that these compounds had promising oral bioavailability features.
Conclusion: The tested compounds need further modification to have significant antimicrobial and antitumor efficacy compared to the reference drugs.

Keywords: anticancer, antimicrobial activity, linear-peptides, Nα-1, 3-benzenedicarbonyl-bis-peptides, molecular docking

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]