BackgroundMulti drug-resistant and mycobacterial infections are a major public health challenge, leading to high mortality and socioeconomic burdens through worldwide. Novel therapeutics are necessary to treat the drug resistant strains, since no new chemical entities are emerged in the last four decades for the treatment of TB.FindingsA series of novel 2-heterostyrylbenzimidazole derivatives were synthesised by cyclisation of (3,4-diaminophenyl)(phenyl)methanone, cinnamic acid using glycerol in high yield. The molecular structures of target compounds (5a–5n) were confirmed by 1H and 13C NMR spectroscopy and mass spectrometry. Newly synthesized compounds were screened for anti-tubercular activity and the MIC was determined against Mycobacterium tuberculosis H37Rv by broth microdilution method using Lowenstein Jensen medium (LJ). These compounds docked into the active site of “Crystal structure of pantothenate synthetase in complex with 2-(2-(benzofuran-2-ylsulfonylcarbamoyl)-5-methoxy-1H-indol-1-yl)acetic acid” (PDB code, 3IVX). Auto dock 4.2 software was used for docking studies.Results 5d, 5e, 5f, 5g, 5i, and 5l show better activity and the most active inhibitor of tuberculosis 5f showed a promising inhibition of M. tuberculosis with MIC value of 16 μg/mL. The molecules functionalized with electron-donating groups (Cl, O, S, etc.) on different aromatic aldehydes (5a–5n) were found to be more active in inhibiting M. tuberculosis. ConclusionsOn the basis of docking studies, 5f has shown good affinity for the enzyme. Comparison was made with the binding energies of the standard drugs amoxicillin (−34.28 kcal/mol) and ciprofloxacin (−28.20 kcal/mol). Among all the designed compounds, the compound 5f shows highest binding energy with two amino acid interactions Lys160, Val187 (−9.80 kcal/mol).

A series of novel indole and pyrimidine scaffolds bearing 1,2,3‐triazoles have been designed and synthesized using click chemistry reaction conditions. Target compounds 9a‐j were synthesized in the multi‐step process. In the first step 5‐substituted‐1‐methyl‐1H‐indole‐3‐carbaldehyde 2a‐b reacted with ethyl cyanoacetate 3 and guanidine hydrochloride 4 in presence of L‐Proline in ethanol undergoes cyclisation to form 5a‐b. Further, 5a‐b condensed with various benzaldehydes to form Schiff's base 6a‐f, which further proporgylated with propargyl bromide to form 7a‐f. Finally, 7a‐f was subjected to click‐chemistry with various azides in the presence of CuSO4.5H2O + sodium ascorbate mixture in Dimethylformamide at room temperature to obtain 2 + 3 cycloaddition products 9a‐j in high yield. All these synthetic methods are mostly green and inexpensive with excellent yields.

A very simple, mild, efficient, and novel green methodology has been developed for the syntheses of some 2-hetero/styrylbenzimidazoles. Title compounds were synthesized by the condensation of -phenylenediamine with cinnamic acids at 150-180 ∘ C for 5-6 h using glycerol containing triacetylborate (10-20 mol%) as the reaction medium. In an alternative approach, condensation of 2-methylbenzimidazole derivatives with aromatic aldehydes was done using glycerol containing triacetylborate (10-20 mol%) as the reaction medium.

A series of novel indole derivatives bearing pyrimidine and cyclic imide scaffolds such as phthalic and maleic anhydrides has been designed and synthesized using both conventional and microwave irradiation (MW) methods under solvent free conditions. The title compounds have been developed by the reaction of 2-aminoo-4-hydroxy-6-(5,1-substituted-indol-3-yl) pyrimidine-5-carbonitrile with phthalic and maleic anhydrides individually using MW method. In addition, these target compounds were also synthesised under conventional heating method. A considerable increase in the reaction rate has been observed with better yields (90-92%) within 2-6 min using microwave irradiation in comparison to conventional thermal treatment.

A novel route was developed for synthesis of high potential 1H‐tetrazoles by using conventional method. Tetrazole scaffold is a promising pharmacophore fragment, frequently used in the development of various novel drugs. Here, the novel (Z)‐3‐(N‐alkyl‐indol‐3‐yl)‐2‐(1H‐tetrazole‐5‐yl)acrylates 5 (a–i) have been synthesized from (Z)‐ethyl‐3‐(1H‐indol‐3‐yl)2‐(1H‐tetrazol‐5‐yl)acrylates 4 (a–c) by using various alkylating agents such as Dimethyl Sulphate (DMS), Diethyl Sulphate (DES), and benzyl chloride; 4 (a–c) were synthesized from sodium azide in the presence of copper sulfate in dimethylformamide; 3 (a–c) have been prepared by Knoevenagel condensation of indole‐3‐carbaldehyde 1 (a–c) and ethylcyanoacetate 2 in the presence of L‐Proline as a catalyst at room temperature in ethanol for an hour. This is an efficient and clean click chemistry method that has various advantages such as easy workup, higher yields, shorter reaction times, and more economical.