Opportunities and challenges of using five‐membered ring compounds as promising antitubercular agents

Abstract

Tuberculosis (TB), a chronic infectious disease, is one of the greatest risks to human beings and 10 million people were diagnosed with TB and 1.6 million died from this disease in 2017. In addition, with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the TB situation has become even worse, which has aggravated the mortality and spread of this disease.To overcome this problem, research into novel antituberculosis agents with enhanced activities against MDR-TB, reduced toxicity, and shortened duration of therapy is of great importance. Fortunately, many novel potential anti-TB drug candidates with five-membered rings, which are most likely to be effective against sensitive and resistant strains, have recently entered clinical trials. Different five-membered rings such as furans, pyranoses, thiazoles, pyrazolines, imidazoles, oxazolidinone, thiazolidins, isoxazoles, triazoles, oxadiazoles, thiadiazoles, and tetrazoles have been designed, prepared, and evaluated for their antimycobacterial activity against Mycobacterium tuberculosis. In this article, we highlight the recent advances made in the discovery of novel five-membered ring compounds and focus on their antitubercular activities, toxicity, structure-activity relationships, and mechanisms of action. K E Y W O R D Santi-TB drug, antitubercular activities, five-membered ring, MDR-TB, tuberculosis

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

“…Moreover, 1,2,3-triazole could form diverse non-covalent interactions, such as hydrogen bonds, van der Waals forces, and dipole-dipole bonds with various enzymes, proteins, and receptors (Bonandi et al, 2017;Bozorov et al, 2019). Hence, 1,2,3-triazole derivatives exhibit a variety of promising biological properties, including antibacterial (Zhang, 2019;Xu, 2020), antimalarial (Chu et al, 2019;Feng et al, 2020), antitubercular (Zhang et al, 2017;Yan et al, 2020), antiviral (Rani et al, 2020;Feng et al, 2021), and anticancer (Lal and Yadav, 2018;Slavova et al, 2020) activities. For example, 1,2,3-triazoles could exert the anticancer potential by inducing the cell cycle arrest and apoptosis of cancer cells.…”

Synthesis of 4‐Chalcogenylated Isoxazoles Mediated by PhICl2 and Diorganyl Disulfides/Diselenides

“…Then, the isolated PhSeCl was applied to react with substrate 1 a under the same conditions and the desired product 2 a was obtained in 85% yield (Scheme 3b). These results implied that the electrophilic R 3 SeCl or R 3 SCl species generated in situ should be the pivotal intermediates for the transformations.…”

Thiazole–Chalcone Hybrids as Prospective Antitubercular and Antiproliferative Agents: Design, Synthesis, Biological, Molecular Docking Studies and In Silico ADME Evaluation

“…The vinyl ketone part of the chalcones is not only responsible for the biological activities of chalcones but is also useful as a key synthon for the preparation of different heterocyclic compounds of pharmacological interest [ 5 ]. Thiazole and chalcone derivatives possess a broad spectrum of bioactivities, including antitubercular [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ], anticancer [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], antioxidant [ 33 , 34 , 35 , 36 , 37 , 38 ], antifungal [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ] and antibacterial [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The nature of the substituents as...…”