The Open Medicinal Chemistry Journal




ISSN: 1874-1045 ― Volume 13, 2019
RESEARCH ARTICLE

Design, Synthesis and Biological Evaluation of Some Triazole Schiff’s Base Derivatives as Potential Antitubercular Agents



Asma A. Sager1, 3, Zainab S. Abood2, Wedad M. El-Amary4, Salah M. Bensaber3, Inass A. Al-Sadawe3, Nouri B. Ermeli2, Salah B. Mohamed1, Mohamed Al-Forgany4, Ibrahim A. Mrema3, Mabrouk Erhuma1, Anton Hermann5, Abdul M. Gbaj1, 3, *
1 National Medical Research Centre, Zawia, Z16, Libya
2 Department of Natural Products, Faculty of Pharmacy, University of Tripoli, Tripoli, Libya
3 Department of Medicinal Chemistry, Faculty of Pharmacy, University of Tripoli, Tripoli, Libya
4 National Center of Infectious diseases, Tripoli, Libya
5 Department of Cell Biology & Physiology, Division of Cellular and Molecular Neurobiology, University of Salzburg, Salzburg, A-5020, Austria

Abstract

Background:

Tuberculosis (TB) is the second important cause of death worldwide caused by a bacterium called Mycobacterium tuberculosis. There is a need to find and develop new Anti-TB medications that are effective, inexpensive and suitable with human immunodeficiency virus and other anti-TB drugs used in many countries and mainly the developing countries where the disease is widespread. These drugs must be designed to shorten treatment time and to be active against resistant forms of the mycobacteria that will help to increase the patients compliance. A key compound which could be used as a lead to meet these requirements, is the thiolactomycin (TLM). This antibiotic which is naturally available has an ability to treat M. tuberculosis by inhibiting condensing enzymes called FAS II (mtFabH, KasA and KasB) which are related to biosynthesis of mycolic acid.

Methods:

Our main aims are to design and synthesize analogues of TLM as new lead molecules which could be a possible anti–TB candidate. To overcome the synthetic challenges associated with preparing the chiral TLM analogues; we synthesized and investigated a series of triazole analogues as inhibitors of KasA enzyme and the whole cell Mycobacteria. A series of twelve compounds were synthesized, purified and fully characterized using several spectroscopic techniques. Molecular modelling studies for our synthesised compounds were achieved by using a modelling program called AutoDock 4.2 utilising rigid docking.

Results:

Our results indicate that analogues of TLM show a good activity as compared to TLM.

Conclusion:

The activity obtained for the synthesized compounds against Mycobacteria tuberculosis indicate that the synthesised compounds 1, 2, 6 and 9 are pharmacologically active as they restrained the growth of the Mycobacteria bacteria.

Keywords: Schiff base, Triazole, Imines, Antitubercular activity, Thiolactomycin analogues, KasA enzyme inhibitors.


Article Information


Identifiers and Pagination:

Year: 2018
Volume: 12
First Page: 48
Last Page: 59
Publisher Id: TOMCJ-12-48
DOI: 10.2174/1874104501812010048

Article History:

Received Date: 15/02/2018
Revision Received Date: 16/04/2018
Acceptance Date: 17/04/2018
Electronic publication date: 30/04/2018
Collection year: 2018

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© 2018 Sager et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4. 0 International Public License (CC-BY 4. 0), a copy of which is available at: https://creativecommons. org/licenses/by/4. 0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this authors at the Department of Genetics and Biochemistry, National Medical Research Centre, Zawia, Z16, Libya, Tel: +218913556785, Fax: +218213405021; E-mails: abdulgbaj1@hotmail.com, ab.Gbaj@uot.edu.ly


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