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Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Evaluation of Cytotoxic, COX Inhibitory, and Antimicrobial Activities of Novel Isoxazole-carboxamide Derivatives

Author(s): Mohammed Hawash*, Nidal Jaradat, Murad Abualhasan, Mohammad Qneibi, Hama Rifai, Tala Saqfelhait, Yaqeen Shqirat, Alaa Nazal, Salam Omarya, Tymaa Ibrahim, Shorooq Sobuh, Abdulraziq Zarour and Ahmed Mousa

Volume 20, Issue 12, 2023

Published on: 23 September, 2022

Page: [1994 - 2002] Pages: 9

DOI: 10.2174/1570180819666220819151002

Price: $65


Isoxazole derivatives are one of the heterocyclic structures that have various biological activities.

Objective: This study aimed to design and synthesize novel isoxazole derivatives and evaluate their cytotoxic, cyclooxygenase (COX) inhibitory, and antimicrobial activities.

Methods: Coupling reactions of aniline derivatives and isoxazole carboxylic acid have been established to synthesize chloro-fluorophenyl-isoxazole carboxamide derivatives. The synthesized compounds were characterized using 1H, 13C-NMR, IR, and HRMS spectrum analysis and evaluated by MTS, COX kit, and antimicrobial microdilution assays.

Results: The synthesized compounds showed moderate to potent cytotoxic activity against all the screened cancer cell lines (except 2b against HepG2) with an IC50 range of 0.107-77.83 μg/ml. The results showed that the most potent compound against cervical cancer cell line (HeLa) was the 2b compound, with an IC50 value of 0.11±0.10 μg/ml, which is less than the IC50 for the potent anticancer drug Doxorubicin. While the 2a and 2b compounds have potential antiproliferative activities against Hep3B with IC50 doses of 2.774±0.53 and 3.621±1.56 μg/ml, respectively. Furthermore, 2c compound was the most active against MCF7, with an IC50 value of 1.59±1.60 μg/ml. In addition, the most potent isoxazole derivative against the COX1 enzyme was the 2b compound, with an IC50 value of 0.391 μg/ml, and compound 2a had a good selectivity ratio of 1.44 compared to the Ketoprofen positive control. However, compound 2c showed antifungal activity against Candida albicans with an MIC value of 2.0 mg/ml in comparison to the antifungal drug Fluconazole (MIC = 1.65 mg/ml).

Conclusion: The synthesized compounds could be candidates for anticancer drugs in the future, and other analogues and cytotoxicity evaluations should be conducted

Keywords: Isoxazole, anticancer, doxorubicin, COX, ketoprofen, antifungal.

Graphical Abstract
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