Pyrrolyl Pyrazoline Carbaldehydes as Enoyl-ACP Reductase Inhibitors: Design, Synthesis and Antitubercular Activity

Abstract

Introduction:In efforts to develop new antitubercular (anti-TB) compounds, herein we describe cytotoxic evaluation of 15 newly synthesized pyrrolyl pyrazoline carbaldehydes.Method & Materials:Surflex-Docking method was used to study binding modes of the compounds at the active site of the enzyme enoyl ACP reductase from Mycobacterium tuberculosis (M. tuberculosis), which plays an important role in FAS-II biosynthetic pathway of M. tuberculosis and also it is an important target for designing novel anti-TB agents.Results:Among the synthesized compounds, compounds 4g and 4i showed H-bonding interactions with MET98, TYR158 and co-factor NAD+, all of which fitted well within the binding pocket of InhA. Also, these compounds have shown the same type of interaction as that of 4TZK ligand. The compounds were further evaluated for preliminary anti-TB activities against M. tuberculosis H37Rv strain.Conclusion:Some compounds were also screened for their mammalian cell toxicity using human lung cancer cell-line (A549) that was found to be nontoxic.

Antimicrobial, Antioxidant, and Anticancer Activities of Some Novel Isoxazole Ring Containing Chalcone and Dihydropyrazole Derivatives

“…Replacement of the methoxy group (26 and 28) with either F (30) or Cl (31) resulted in a drop in the antioxidant activity, which suggested that electron-donating groups are favored at positions 2 on the phenyl ring. A similar phenomenon was observed in the dihydropyrazole series (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). Compound 43 was found to have an IC 50 of 6 µg/mL and was the most potent in this series.…”

“…The crude precipitate was recrystallized using chloroform to afford chalcones 17-31. The target dihydropyrazoles (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) were obtained by treating the synthesized chalcones with semicarbazide in a catalytic amount of pyridine and purified using silica gel column chromatography.…”

“…Hence, we decided to screen our compounds for antibacterial, antifungal, antioxidant, and anticancer (prostrate cell line) activities. The target chalcones (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) and pyrazolines (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) were tested for their antimicrobial activities by serial tube dilution method against two types of bacterial and fungal strains (Tables 1 and 2). The bacterial strains used for the testing, including Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, whereas the fungal strains employed were Aspergillus niger and Candida tropicalis.…”

Synthesis, characterization and antitubercular evaluation of some new isoxazole appended 1-carboxamido-4,5-dihydro-1H-pyrazoles

“…Pyrazolines possess sundry of activities including antimicrobial [7][8][9], anticancer [10][11][12], antioxidant [13], antiamoebic [14], antiinflammatory [15], antidiabetic [16], diuretic [17] and carbonic anhydrase inhibition [18]. One of the extensively studied activities of dihydropyrazole-1-carboxamides is their antitubercular ability against different Mycobacterium species [19][20][21][22][23][24]. This may be due to the fact that the pyrazoline contains carbohydrazide portion which is also found in the most commonly used antitubercular drug, Isoniazid.…”

Design, Synthesis, and Anti-mycobacterial Evaluation of New 3,5-Disubstituted-pyrazole-1-carbothioamides

“…In 2006, Corbett et al reported that the emergence of anti-TB resistance and HIV are vital contributors to death by TB [3]. Recently, several drugs in the market were used for TB treatment, including isoniazid (INH), rifampicin, pyrazinamide, and delamanid, all of which possess a nitrogen atom in their ring structure [4]. The problem is commonly known that Mycobacterium tuberculosis (MTB) has developed resistance to any of these drugs [5].…”