A new series of naphthyl chalcones (3a–3p) and their pyrazoline derivatives (4a–4h) were synthesized using substituted acetophenones, substituted naphthaldehydes, and hydrazine hydrate as starting materials. All the synthesized compounds were characterized by IR, NMR, and mass spectrometric analysis and screened for antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27924) and antibacterial activity against Staphylococcus aureus (MTCC 96), Bacillus subtilis (MTCC 441), Escherichia coli (MTCC 443) and Klebsiella pneumonia (MTCC 109). Compounds 3b and 3p exhibited significant antibacterial activity against all the tested bacterial strains. Amongst the synthesized compounds, compound 4b with 2-hydroxy-5-bromophenyl substitution at 3rd position of pyrazoline showed significant antimycobacterial activity with MIC of 6.25 µM comparable to that of standard isoniazid. The synthesized compounds were further screened for their cytotoxic activity against the MDA-MB-231 and SKOV3 cell lines. The compounds 3a, 3l, 4b, 4c, 4e, and 4h did not exhibit any cytotoxicity, and other compounds exhibited IC₅₀ values higher than 8 and 22 µM against MDA-MB-231 and SKOV3 cell lines, respectively, compared to 1.20 and 1.30 µM shown by standard doxorubicin. To find out the putative binding mode of significantly active and weakly active compounds, a molecular docking study was also performed. In that, the most active compound 4b, displayed a hydrogen bond interaction with docking score of −10.50 kcal/mol and energy of −44.50 weakly active compound 3h did not show any crucial hydrogen bond interaction with the surrounded amino-acid residues and revealed a docking score of −6.74 and docking energy of −42.50.

中文翻译：

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设计，合成，计算机模拟研究和评估新型查尔酮及其吡唑啉衍生物的抗菌和抗结核活性

以取代的苯乙酮，取代的萘乙醛和水合肼为起始原料合成了一系列新的萘基查耳酮（3a - 3p）及其吡唑啉衍生物（4a - 4h）。所有合成的化合物均通过IR，NMR和质谱分析进行表征，并筛选出针对结核分枝杆菌H37Rv（ATCC 27924）的抗分枝杆菌活性和对金黄色葡萄球菌（MTCC 96），枯草芽孢杆菌（MTCC 441），大肠杆菌（MTCC ）的抗菌活性443）和克雷伯菌肺炎（MTCC 109）。化合物3b和3p对所有测试的细菌菌株显示出显着的抗菌活性。在合成的化合物中，在吡唑啉第3位具有2-羟基-5-溴苯基取代的化合物4b具有显着的抗分枝杆菌活性，MIC为6.25 µM，与标准异烟肼相当。进一步筛选合成的化合物对MDA-MB-231和SKOV3细胞系的细胞毒活性。化合物3a，3l，4b，4c，4e和4h不显示任何细胞毒性，其他化合物显示IC ₅₀与标准阿霉素显示的1.20和1.30 µM相比，针对MDA-MB-231和SKOV3细胞系的Ms值分别高于8和22 µM。为了找出显着活性和弱活性化合物的假定结合模式，还进行了分子对接研究。活性最高的化合物4b表现出氢键相互作用，对接得分为-10.50 kcal / mol，能量为-44.50弱活性化合物3h没有显示出与周围氨基酸残基的关键氢键相互作用，并显示出对接得分为-6.74，对接能量为-42.50。