1,3‐Oxazole‐isoniazid hybrids: Synthesis, antitubercular activity, and their docking studies

Abstract

A series of novel N′‐([2‐aryl‐5‐methyl‐1,3‐oxazole‐4‐yl]methylene)isonicotino/nicotino hydrazides 10a‐l were prepared by the condensation reaction of 2‐aryl‐5‐methyl‐1,3‐oxazole‐4‐carbaldehydes 8a‐f with the corresponding isonicotino/nicotino hydrazides 9a/9b. The structures of the new compounds were elucidated by various spectroanalytical techniques, including IR, 1H NMR, 13C NMR, elemental (C,H,N), and mass analysis. All the newly prepared INH‐1,3‐oxazole hybrids were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. Among all the synthesized hybrids, compounds 10c and 10i derivatives displayed highest antitubercular activity with minimal inhibitory concentration 1.56 μg/mL. Further, molecular docking studies against the InhA enzyme were carried out to understand the interactions between potent hybrids and the target enzyme. Thus, these kind hybrids have the potentiality for the discovery of new antitubercular agents for deployment in the control and eradication of tuberculosis.

Updated Information on Antimicrobial Activity of Hydrazide–Hydrazones

“…The authors discovered that compounds bearing methoxy groups in the phenyl ring attached to the 1,3-oxazole scaffold displayed better activity compared to the other compounds (Figure 32). Synthesized substances (40,41) were tested in vitro for cytotoxicity in human embryonic kidney (HEK-293T) cells and did not display changes in cytotoxicity as compared with vehicle (DMSO) [42].…”

Synthesis, Biological Evaluation and Docking Studies of 4H‐[1,2,3] thiadiazolo[4,5‐b]indole Hybrids as Antifungal Agents

“…[2] Additionally, these compounds serve as corrosion inhibitors, fungicides, photo stabilisers, sanitizers, antioxidants, fluorescents, flavourings and copolymers. [3] They exhibit a wide range of biological activity, including antifungal, [4] antiinflammatory, [5] anti-bacterial, anti-cancer, [6,7] anti-tubercular, [8] and anticonvulsant, [9] analgesic, [10] anti-malarial, [11] anti-viral, [12] anti-protozoal, [13] and anti-HIV. [14] By heterocyclic compounds, it is possible to change the solubility, lipophilicity, polarity, and hydrogen bonding capabilities of biologically active compounds, which improves the ADME/Tox characteristics of medications or drug candidates.…”

Benzimidazole‐1,3,4‐Oxadiazole Hybrids: Synthesis, Anticancer Evaluation, Docking and DFT Studies

“…[23][24] It is reported that combination of different bioactive heterocycles in a candidate have resulted in enhanced therapeutic activities with diverse mode of actions on various biological targets. For example, biologically active 1,3-oxazole containing isoniazid hybrid have shown promising antitubercular activity, [25] Katariya et al reported quinoline-hydrazone hybrid [26] and 1,3-oxazole banged pyridyl-pyrazolines [27] as potential cytotoxic agents, Quinoline-1,3-oxazole hybrid reported by Shah et al displayed significant cytotoxicity against various cell lines. [28] In recent years, molecular docking and DFT studies have gain considerable importance as these studies are helpful in exploring the relationship between geometry and organic, inorganic molecules electronic properties which gives information about the binding interactions of the molecules with the target protein.…”

“…It is reported that combination of different bioactive heterocycles in a candidate have resulted in enhanced therapeutic activities with diverse mode of actions on various biological targets. For example, biologically active 1,3‐oxazole containing isoniazid hybrid have shown promising antitubercular activity, [25] Katariya et al reported quinoline‐hydrazone hybrid [26] and 1,3‐oxazole banged pyridyl‐pyrazolines [27] as potential cytotoxic agents, Quinoline‐1,3‐oxazole hybrid reported by Shah et al displayed significant cytotoxicity against various cell lines [28] …”