Abstract A novel series of pyrazoline incorporated isoxazole derivatives were designed and synthesized. The synthesized compounds were characterized by 1 H NMR, IR and ESI-MS spectra. In addition, all the synthesized compounds were docked with the target human DHFR (PDB ID: 1KMS). Among all the compounds, compound 5-(4-methoxyphenyl)-3-(5-methyl-3-(4-nitrophenyl)isoxazol-4-yl)-4,5-dihydro-1 H -pyrazol-1-yl)(phenyl)methanone proved to be the most potent exhibiting the highest binding affinity with a docking score of 153.763. All the synthesized compounds were screened for anticancer activity against human breast cancer cell lines MCF-7 and MDA-MB-231 through MTT assay. Out of all the synthesized compounds (5-(4-methoxyphenyl)-3-(5-methyl-3-(4-nitrophenyl)isoxazol-4-yl)-4,5-dihydro-1 H -pyrazol-1-yl)(phenyl)methanone posses good activity with IC 50 values ranging from 3–4 μg/mL. Further all the compounds were screened for antitubercular assay against the strain H 37 Rv and multidrug resistant strain DKU 156, among all four compounds exhibited significant activity at 6.25 µg/mL concentrations. Thus the MIC value may be in between the range of 3.12 and 6.25 µg/mL.

中文翻译：

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掺入吡唑啉的异恶唑衍生物的设计、合成、分子对接研究和生物学评价

摘要 设计并合成了一系列新型吡唑啉类异恶唑衍生物。合成的化合物通过 1 H NMR、IR 和 ESI-MS 光谱进行表征。此外，所有合成的化合物都与目标人DHFR（PDB ID：1KMS）对接。在所有化合物中，化合物5-(4-甲氧基苯基)-3-(5-甲基-3-(4-硝基苯基)异恶唑-4-基)-4,5-二氢-1H-吡唑-1-基) （苯基）甲酮被证明是最有效的，具有最高的结合亲和力，对接评分为 153.763。所有合成的化合物均通过 MTT 法筛选对人乳腺癌细胞系 MCF-7 和 MDA-MB-231 的抗癌活性。在所有合成的化合物中（5-（4-甲氧基苯基）-3-（5-甲基-3-（4-硝基苯基）异恶唑-4-基）-4，5-dihydro-1 H -pyrazol-1-yl)(phenyl)methanone 具有良好的活性，IC 50 值范围为 3–4 μg/mL。此外，针对 H 37 Rv 菌株和多药耐药菌株 DKU 156 的抗结核试验筛选了所有化合物，其中所有四种化合物在 6.25 µg/mL 浓度下均表现出显着活性。因此，MIC 值可能介于 3.12 和 6.25 µg/mL 之间。