Design, synthesis, and biological evaluation of benzo[d]imidazole-2-carboxamides as new anti-TB agents

Dhameliya, Tejas M.; Patel, Kshitij I.; Tiwari, Rishu; Vagolu, Siva Krishna; Panda, Dulal; Sriram, Dharmarajan; Chakraborti, Asit K.

doi:10.1016/j.bioorg.2020.104538

Cited by 34 publications

(14 citation statements)

References 66 publications

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“…The synthesis of nitrogen- and oxygen-containing scaffolds has gained momentum [ 11 – 15 ] due to their versatility in the arsenal of drug discovery [ 16 – 18 ]. Oxadiazoles, being five-membered heterocyclic scaffold with an oxygen and two nitrogen atoms constitute four regioisomeric structures such as 1,2,3-oxadiazole, 1,2,5-oxadiazole, 1,2,4-oxadiazole and 1,3,4-oxadiazole.…”

Section: -Oxadiazoles As Important Heterocyclic Scaffoldsmentioning

confidence: 99%

“…Several nitrogen- and oxygen-containing scaffolds have been found of much interest due to their potential as anti-mycobacterial agents [ 15 , 17 , 18 , 61 – 63 ]. In this regard, Upare and coworkers reported the anti-tubercular activity of ( E )-3-alkyl-5-styryl 1,2,4-oxadiazoles [ 48 ].…”

Section: Synthetic Account Of 124-oxadizoles With Anti-infective Activitymentioning

confidence: 99%

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A review on synthetic account of 1,2,4-oxadiazoles as anti-infective agents

et al. 2022

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Graphical abstract Most of the currently marketed drugs consist of heterocyclic scaffolds containing nitrogen and or oxygen as heteroatoms in their structures. Several research groups have synthesized diversely substituted 1,2,4-oxadiazoles as anti-infective agents having anti-bacterial, anti-viral, anti-leishmanial, etc. activities. For the first time, the present review article will provide the coverage of synthetic account of 1,2,4-oxadiazoles as anti-infective agents along with their potential for SAR, activity potential, promising target for mode of action. The efforts have been made to provide the chemical intuitions to the reader to design new chemical entity with potential of anti-infective activity. This review will mark the impact as the valuable, comprehensive and pioneered work along with the library of synthetic strategies for the organic and medicinal chemists for further refinement of 1,2,4-oxadiazole as anti-infective agents.

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Section: -Oxadiazoles As Important Heterocyclic Scaffoldsmentioning

confidence: 99%

Section: Synthetic Account Of 124-oxadizoles With Anti-infective Activitymentioning

confidence: 99%

A review on synthetic account of 1,2,4-oxadiazoles as anti-infective agents

et al. 2022

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“…[18] On the another part, the innovative and green synthetic strategies have given a new era of synthesis of diversely substituted heterocycles. [19][20][21] Towards the on-going research endeveour on anti-TB agents, [22][23][24][25][26][27][28][29] recently we have reported the quinquennial account of diverse scaffolds in search of agents having anti-TB profile reported during 2016-2020. [30] In this review, we have shed light on candidates having anti-TB activity (minimum inhibitory concentration, MIC or hald maximal inhibitory concentrationm IC 50 of 20 μg/mL or μM) reported during 2021 retrieved through Sci-Finder [31] to educate the reader of the present work to update with the on-going trends on design of newly identified anti-tubercular agents.…”

Section: Diverse Scaffolds Reported For Anti-tb Activitymentioning

confidence: 99%

Comprehensive Coverage on Anti‐mycobacterial Endeavour Reported in 2021

et al. 2022

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Tuberculosis (TB) has been the highly contagious airborne disease caused by Mycobacterium tuberculosis and the major leading infectious disease with the higher upsurge of morbidity and mortality. Owing to problems in the current regimen for TB and emergence of drug resistance strains, there is a strong necessity for development of new anti-TB drugs with better efficacy, reduced duration of action, along with improved patient compliance. Towards this, the scaffolds reported in 2021 with anti-tubercular activity such as benzofuran, benzothiazinone, benzimidazoles, indole, piperidine, piperazine, pyrazole, pyridine, pyrimidine, pyrrolidine, quinoxaline, triazole, etc. have been critically reviewed along with their structureactivity relationships, mode of actions with anticipations of intuitions to design the newer anti-mycobacterial scaffolds.The present work provide the organized coverage of diversified scaffolds with anti-tubercular profile reported in 2021 along with the insightful discussion on their merits and demerits. The mode of anti-tubercular action against Mycobacterium tuberculosis strains have been presented keeping in mind the novel drug candidates against drug resistant strains [a] Dr.

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“…Further, plethora of compounds bearing amide or carboxamides moieties have been reported for anti-TB activity. [16][17][18][19][20][21][22][23] Recently, benzazoles-2-carboxamides including benzo[d]thiazole-2-caboxamides [24][25][26] and benzo[d]imidazole-2carboxamides [27] have been identified as key pharmacophoric scaffold for anti-TB activity. Among these heterocyclic benzazoles, indole should not be undermined due to the potential anti-TB activity as several research groups have focused on discovery of substituted indole as potent anti-mycobacterial agents.…”

Section: Designmentioning

confidence: 99%

“…the key intermediate for the synthesis of indole-2-carboxamides (6), has been achieved by the cyclocondensation of phenyl hydrazine hydrochloride (1) with ethyl pyruvate (2) using ptosylic acid in catalytic amount (10 mol %) in ethanol under reflux (Scheme 1). [31] The nucleophilic acyl substitution of indole-2-carboxylate (3) with benzylamine (4a, 2 mmol) have been tried using ammonium chloride NH 4 Cl (10 mol %), to form indole-2-carboxamide (5a) under neat conditions (Scheme 1) by adopting the green chemistry approach at 100 °C for 12 h. [24,25,27] However, the starting material has been recovered without formation of any new spot on the TLC. Further, we failed to get the product even when we attempted the same reaction in ethanol.…”

Section: Chemistryselectmentioning

confidence: 99%

Indole‐2‐carboxamides as New Anti‐Mycobacterial Agents: Design, Synthesis, Biological Evaluation and Molecular Modeling against mmpL3

Bhakhar¹,

Vaghela²,

Varakala

et al. 2022

ChemistrySelect

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Tuberculosis (TB), an airborne disease caused by Mycobacterium tuberculosis, has infected millions of people and been responsible for their deaths. Toward the anti‐TB endeavor, the synthesis of total twenty‐four indole‐2‐carboxamide derivatives as potent anti‐TB agents have been carried out using CDI‐mediated amidation. The biological evaluation against H37Rv revealed compounds 5d, 5e and 5u with MICs in the range of 3.125‐12.5 μg/mL using MABA assay. Further, compound 5u was tested against RAW 264.7 cell by MTT assay and showed 32 % growth inhibitions. The structure activity relationship of the indole‐2‐carboxamides has been established for antimycobacterial activity. The physicochemical properties and ADMET parameters of the 5d, 5e and 5u using pKCSM and SwissADME revealed their suitability as promising drug candidates. Molecular docking studies using AutoDock Vina revealed binding of 5u with the catalytic site of mmpL3 (PDB ID: 6AJG). The MD simulations of the most active compound 5u using GROMACS 2020.1 revealed its stability at the protein active site. Further optimization of indole‐2‐carboxamies may reveal the potentiation of identified anti‐mycobacterial drug candidates.

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Design, synthesis, and biological evaluation of benzo[d]imidazole-2-carboxamides as new anti-TB agents

Cited by 34 publications

References 66 publications

A review on synthetic account of 1,2,4-oxadiazoles as anti-infective agents

A review on synthetic account of 1,2,4-oxadiazoles as anti-infective agents

Comprehensive Coverage on Anti‐mycobacterial Endeavour Reported in 2021

Indole‐2‐carboxamides as New Anti‐Mycobacterial Agents: Design, Synthesis, Biological Evaluation and Molecular Modeling against mmpL3

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