Chemical Classes Presenting Novel Antituberculosis Agents Currently in Different Phases of Drug Development: A 2010–2020 Review

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a curable airborne disease currently treated using a drug regimen consisting of four drugs. Global TB control has been a persistent challenge for many decades due to the emergence of drug-resistant Mtb strains. The duration and complexity of TB treatment are the main issues leading to treatment failures. Other challenges faced by currently deployed TB regimens include drug-drug interactions, miss-matched pharmacokinetics parameters of drugs in a regimen, and lack of activity against slow replicating sub-population. These challenges underpin the continuous search for novel TB drugs and treatment regimens. This review summarizes new TB drugs/drug candidates under development with emphasis on their chemical classes, biological targets, mode of resistance generation, and pharmacokinetic properties. As effective TB treatment requires a combination of drugs, the issue of drug-drug interaction is, therefore, of great concern; herein, we have compiled drug-drug interaction reports, as well as efficacy reports for drug combinations studies involving antitubercular agents in clinical development.

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“…We used the data of preventive examinations in each age group, as well as analyzed the results of the survey of girls on the appeal. The examination included an assessment of the skin and visible mucous membranes, upper and lower extremities, organs of the genitourinary system, anorectal region, and oropharynx [22,23]. Towards to determination of the state of the abdominal cavity and pelvic organs, palpation of the anterior abdominal wall and rectoabdominal/bimanual examination and hardware methods of investigation were performed.…”

Comprehensive Coverage on Anti‐mycobacterial Endeavour Reported in 2021

“…Vijayakumar et al have designed the novel benzhydryl piperazine-coupled nitrobenzenesulfonamide hybrids (11)(12)(13)(14)(15)(16)(17)(18) via molecular hybridization of benzhydrylpiperazine, amino acids, and nitrobenzenesulfonamide and revealed total eight derivatives with MICs of 0.78 μg/mL (Figure 6). [42] The MICs of these compounds were compared with isoniazid (0.05 μg/mL), ethambutol (1.56 μg/mL) and comparable with rifampicin (0.10 μg/mL).…”

“…Due to ineffectiveness of the currently used anti-TB regimen in curbing resistant strains and genetic modification of causative agent has heightened development of new drug moeities with more efficacious, less toxicity with shorter duration of treatment. [13,14] Several innovative strategies have been adopted for the development of novel anti-TB agents such as development of new chemical entities with different mechanisms of action and cytotoxic levels, [15,16] merging of pharmacophores (hybrid analogs), [17] and improving pharmacological profile of existing drugs. [18] On the another part, the innovative and green synthetic strategies have given a new era of synthesis of diversely substituted heterocycles.…”

Design, Synthesis and In Vitro Antimicrobial Activity of 6-(1H-Benzimidazol-2-yl)-3,5-dimethyl-4-oxo-2-thio-3,4-dihydrothieno[2,3-d]pyrimidines

“…It was also claimed that 4-amino-thieno [2,3-d]pyrimidine are the new scaffolds of the selective inhibitors of the QcrB subunit of the electron transport chain enzyme cytochrome bc1, which is a novel target for antitubercular agents [19]. The inhibition of QcrB results in the blockade of oxidative phosphorylation, which leads to the total death of M. tuberculosis cells [20].…”

“…antitubercular agents [19]. The inhibition of QcrB results in the blockade of oxidative phosphorylation, which leads to the total death of M. tuberculosis cells [20].…”