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

Abstract

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. TB is a global problem and is one of the major culprits responsible for the death of many in the developing world despite the availability of more than 20 drugs. Hence, there is an imperative need for the development of novel antitubercular drugs. To develop better agents against tuberculosis, we synthesized a series of dihydropyrazole-1-carboxamides by the base-catalyzed condensation of isoxazolyl chalcones with semicarbazide. The compounds were purified by column chromatography and characterized by spectral methods including IR, 1 H NMR, 13 C NMR and elemental analysis. The antitubercular activity was screened against Mycobacterium tuberculosis by MABA assay where isoniazid was used as positive control for comparing the activity. The studies revealed that isoxazole-1-carboxamides were more active compared to the corresponding chalcones. Substituents on the phenyl ring at position-5 of isoxazole ring played a crucial role in determining the antitubercular potency. The compounds 4n and 4o containing a blend of halogen and methoxyl groups at ortho and para positions of phenyl ring showed potency greater than the standard, isoniazid with MIC of 0.1 µg/mL and emerged as promising leads against TB. Further, 4n and 4o were assessed for their cytotoxic effects on L02 (human normal cell line) by using MTT assay. The compounds showed no cytotoxicity and established the safety of these compounds.

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

“…The synthesis and characterization of compounds 17-31 and 32-46 has been published previously [9,11]. Chalcones (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) were prepared by Claisen-Schmidt condensation reaction (Scheme 1) in the presence of aqueous potassium hydroxide as a catalyst.…”

“…Chalcones (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) were prepared by Claisen-Schmidt condensation reaction (Scheme 1) in the presence of aqueous potassium hydroxide as a catalyst. The 1-(isoxazole-5-yl)ethanone (1) was condensed with substituted benzaldehyde (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) under basis conditions at room temperature for 24 h. The reaction was stopped by transferring the mixture on ice. The crude precipitate was recrystallized using chloroform to afford chalcones 17-31.…”

“…A literature survey on chalcones revealed that compounds containing heteroaromatic rings in their aryl portion showed excellent biological profiles [7,8]. We have previously reported heterocyclic ring-appended chalcones exhibiting antitubercular, antifungal, and cytotoxic activities [9][10][11][12][13]. Based on a literature survey [1][2][3][4][5] and our previously conducted studies [9][10][11][12][13], we herein report a continuation of that work, with a goal of further evaluating isoxazole-containing chalcones and its dihydropyrazole derivatives (privileged heterocyclic compounds) ( Figure 2) for their antibacterial, antifungal, antioxidant, and anticancer activities.…”

“…We have previously reported heterocyclic ring-appended chalcones exhibiting antitubercular, antifungal, and cytotoxic activities [9][10][11][12][13]. Based on a literature survey [1][2][3][4][5] and our previously conducted studies [9][10][11][12][13], we herein report a continuation of that work, with a goal of further evaluating isoxazole-containing chalcones and its dihydropyrazole derivatives (privileged heterocyclic compounds) ( Figure 2) for their antibacterial, antifungal, antioxidant, and anticancer activities. The results of these efforts and the structure- Chalcones, a privileged structure in medicinal chemistry [6], are a type of open chain flavonoids bearing two aryl rings connected through a three-carbon spacer, the propenone linkage.…”

Synthesis and Biological Evaluation of Some Novel Mannich Bases of Isoxazoline Derivatives as Possible Antimicrobial Agents

“…After this time, 25µL of freshly prepared 1:1 mixture of Almar Blue reagent and 10 % Tween 80 was added to the plate and incubated for 24 h. A blue colour in the well was interpreted as no bacterial growth and pink colour was scored as growth. The MIC was defined as lowest drug concentration which prevented the colour change from blue to pink [23][24][25].…”