Many researches are undertaken to develop antibiotics to treat resistant tuberculosis. This review discusses new trends in research undertaken on new antituberculars reported to date, with a particular attention on their synthesis and analysis.
Tuberculosis still remains a major worldwide Public health concern [
Recently, two new compounds, bedaquiline and delamanid were approved in combination to the actual MDR-TB chemotherapy [
To face the multifactorial grow in tuberculosis epidemiology leading to an economical impact there is an emergency to discover and develop new antibiotics with new mechanisms of action having one target and less toxicity [
This study explored and discussed strategies developed in the recent pass in synthesis and analysis of new antibubercular compounds.
Tuberculosis (TB) is one of the oldest human diseases, but not a disease of the past. The discovery of Mycobacterium tuberculosis as the etiologic agent of tuberculosis has accelerated research and development of treatment and prevention of this disease. In 1921, the TB vaccine bacillus Calmette-Guerin (BCG) was firstly used in clinics. After the discovery of streptomycin as the first antituberculosis drug in 1944, many other antituberculosis drugs were then developed, e.g. isoniazid, rifampicin, ethambutol and pyrazinamide. Consequently, quadri-therapy regimens have been started for the treatment of TB in 1967. Tuberculosis became curable by chemotherapy and for that reason many people have believed that this disease could almost be defeated. Unfortunately, in the mid-80s, with the epidemic of acquired immune deficiency syndrome (AIDS), Tuberculosis has returned as one of the most threatening infectious diseases.
The current treatment regimen of Tuberculosis has some limitations. Decades of widespread and uncontrolled application of antibiotics in clinical has resulted in the emergence of drug resistant strains of Mucobacterium tuberculosis [
Scheme 1. General structure of potential antituberculars containing Phenothiazine nucleus [
Many studies of Quinoxalines showed interesting biological properties and the structure-activity relationship (SAR), good Mycobacterium tuberculosis activity and less reduction potentials but little is known about their mechanism of action [
Scheme 2. General structure of quinoxalines [
Isoniazid and quinolones are combined by multicomponent cyclocondensation to give new active and less toxic potential antituberculars but the mechanism of action is not discussed [
Scheme 3. General structure of biquinolone-isoniazide hybrids [
Fatty acid biosynthesis enzyme inhibitors appear to be attractive molecules for the design of news antitubercular agents but only in vitro [
Scheme 4. Antitubercular compounds of Pisonia umbellifera [
Azoles inhibit the lipid biosynthesis of the cell-wall of the pathogen agents made of complex fatty acids like mycocerosic acids, arabinogalactans and peptidoglycans are lipophilic, and this key property influences their ability to reach their target by transmembrane diffusion and show promising activity against drug resistant tuberculosis. Clubbed 1, 2, 4-triazoles and 1, 3, 4-oxadiazoles are new class of azole antituberculars that are proved to be highly active both in vitro and in vivo. Propylthiazoles coupled with other heterocyclic rings provide novel biologically active compounds that could be explored as potent antimicrobial and antitubercular agents. The study was limited to the preliminary step of cytotoxicity, antimicrobial and antitubercular activities [
Scheme 5. General Strutucres of antitubercular Oxazoles, Thiadiazoles and triazoles compounds synthesized [
An important aspect is that the presence of nitro-imidazole ring in antibiotics influences reduction and the stability of the corresponding nitro radical anion and tend to be a key element to overcome the resistance of bacteria [
Scheme 6. Structures of antitubercular Nitroimidazoles [
Imidazole [1, 2-a] pyridine inhibitors compounds of resistant antituberculosis pathogens inhibiting the DNA synthesis are also explored and further investigation are needed for confirmation [
Scheme 7. New Imidazole [1, 2α] pyridine inhibitors [
Microwave assisted synthesis can improve reaction yields in less time and friendly to the environment comparatively to traditional heating method [
Scheme 8. General structure of Microwaze-Assisted Synthesized new antitubercular Quinoxaline-Incorporated Schiff Bases [
Benzimidazole compound are not only none cytotoxic but also release good antitubercular activities, and one of them is shown to give better activity than chloramphenicol and ketoconazole but the tested cytotoxic of these molecules is none neglected [
Scheme 9. General structure of Facile Synthesized Benzimidazole bearing 2 pyridones new antituberculars compounds [
The shikimate kinase inhibition is a newly discovered mechanism of action of some new antitubercular medicines, results are limited to in silico-designs until, and in vitro tests and clinical trials are needed for a final conclusion [
Concerning methods used for antitubercular analysis, HPLC-RRS was reported to be a suitable method to detect fluoroquinolones in human urine and in water [
We have critically examined the strategies developed in the last decades for antibubercular compounds synthesis and analysis. Decades of widespread and uncontrolled application of antibiotics in clinical has resulted in the emergence of drug resistant strains of M. tuberculosis. To face drug resistance, several methods are developed for the synthesis of new antitubercular compounds. Among many strategies that are actually used in the drug development, fragment-based drug discovery (FBDD) approach has emerged as a promising strategy. Azoles are more discussed than any other antitubercular. Many analytical methods are used to characterize antitubercular antibiotics. Liquid chromatography and voltammetry are mostly preferred for the determination of antitubercular compounds. The redox (oxidation/reduction) properties of antituberculars make them analyzable by electrochemical methods. The quantification of the categories of antibiotics by voltammetry in both dosages forms and human body fluids seems to be the cheapest for developing countries. This analytical method is not only precise, accurate and with low limit of detection but also less difficult to perform comparably to the others.
The authors declare no conflicts of interest regarding the publication of this paper.
Dackouo, B. and Arama, D.P. (2019) Systematic Review of New Trends in Antitubercular Synthesis and Analysis. Journal of Materials Science and Chemical Engineering, 7, 1-9. https://doi.org/10.4236/msce.2019.71001