Synthesis, Antimicrobial, Antitubercular and Cheminformatic Studies of 2-(1-Benzofuran-2-Yl)-N'-[(3z)-2-Oxo-1, 2-Dihydro-3h-Indol-3-Ylidene] Quinoline-4-Carbohydrazide and Its Derivatives

Abstract

Objective: Synthesis of novel 2-(1-benzofuran-2-yl)-N'-[(3Z)-2-oxo-1, 2-dihydro-3H-indol-3-ylidene] quinoline-4-carbohydrazide and its derivatives for antimicrobial and antitubercular activity.Methods: Synthesis was carried out using the general method and the structures were confirmed by IR, 1 Results:The results revealed that at 25 mg/ml concentration, compounds 3a and 5a showed good antibacterial activity at 3.5±0.1, 3.8±0.3, 3.6±0.2 respectively against E. coli, K. pneumonia and S. typhimurium, when compared with drug streptomycin with similar concentration. The percentage of inhibition found at 50 µg/ml concentration, compounds 2b and 6a exhibited good antifungal activity at 53±1.15, 57±1.52 against A. flavus and C. neoformans, compared with standard drug fluconazole. The increase in activity was found to be dose dependent. The analogue 2a showed good antitubercular activity at 12.5±0.5 µg/ml, compounds 2b, 3a, 4a-b, 5a-b and 6a-b exhibited significant activity at 25±0.57 µg/ml and compound 3b showed moderate activity at 50±0.57 µg/ml. The mean value of P<0.05 were considered to be statistically significant. The absorption, distribution, metabolism, excretion and toxicity studies of the entitled molecules were analyzed and found to be in acceptable range.H-NMR, [13]C-NMR and mass spectral analysis. The antibacterial activity was carried by agar well diffusion method, antifungal activity was performed by poison food technique and antitubercular activity was carried out by Microplate Alamar Blue Assay (MABA) method with the help of H37Rv. In silico absorption, distribution, metabolism, excretion, toxicity (ADMET) study of the drug, likeliness was carried out in ACD/lab-2. Conclusion:The study reveals that compounds containing benzofuran coupled nitrogen heterocycles are essential for activity as they possess excellent drug-like characteristics, suggesting to be potentially best inhibitor of H37Rv strain. The in silico ADME analysis also revealed that all the compounds were in acceptable range to obey the pharmacokinetic parameters.

Creation, Physical and Chemical Properties of Alkil-2-((5-Phenethyl-4-R-1,2,4- Triazole-3-Yl)thio)acet(propan,benz)imidates

“…Synthesized alkil-2-((5-phenethyl-4-R-1,2,4-triazole-3-yl)thio) acet(propan,benz)imidates (compounds 5-15, Tables 1-3) are brown (6,7,8,11,15), white (9, 13), yellow (10,14) or grey (12) amorphous substances, soluble in organic solvents and slightly soluble in water. Target compounds were recrystallized from ethanol for the analysis.…”

“…This problem consists of a shortage of cheap national medicines, which has not its own side effects. The literature analysis of the last years about 1,2,4-triazole derivatives shows the intensive growth of bibliographic sources number [1][2][3][4][5][6][7]. Currently, the works of azole nitrogen compounds have been progressively getting people's attention and have been published, owing to their functionality and the wide range of the practical application [8][9][10].…”

“…1,2,4-Triazoles are one very significant class of compounds for treating many types of diseases. For example, voriconazole, itraconazole, fluconazole, saperconazole, and other medicines with different biological activity [1][2][3][4][5][6][7][8]. Based on this, it was synthesized 1,2,4-triazole derivatives as new potential biological active substances.…”

“…According to the results of previous research, the purpose of our experiment is the creation and the establishment of physical-chemical properties of new highly efficient and low-toxic substances, namely alkil-2-((5-phenethyl-4-R-1,2,4-triazole-3-yl)thio)acet(propan,benz)imidates. (6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were considered according to the methods described in the State Pharmacopeia of Ukraine [13,14]. Melting point was measured by the capillary method (2.2.14).…”

Isatin Derivatives with Potential Antitubercular Activities

“…investigated the anti‐TB activities of 10 isatin‐quinoline hybrids 11 (Fig. ), and all of them possessed good anti‐TB activities . The SAR suggested that unsubstituted hybrid was more potent than those with ─F, ─Cl, ─Br, and ─NO 2 substituted isatin moieties at C‐5 position.…”