Journal of the Iranian Chemical Society ( IF 2.2 ) Pub Date : 2022-02-09 , DOI: 10.1007/s13738-022-02495-x Mohammad M. Ibrahim 1 , Hasan Abumahmoud 1 , Abdullah T. Al-Fawwaz 2
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In the present study, a new series of 3-(2,5-dichlorothiophen-3-yl)-5-aryl-4,5-dihydro-1H-pyrazole-1-carbothioamides 2 were synthesized either by the reaction of (E)-3-aryl-1-(2,5-dichlorothiophen-3-yl)prop-2-en-1-ones 1 with thiosemicarbazide or by one-pot reaction of 3-acetyl-2,5-dichlorothiophene with the corresponding aldehyde and thiosemicarbazide. Additionally, 2-(3-(2,5-dichlorothiophen-3-yl)-5-aryl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles 3 were synthesized in 46–89% yields by the reflux of carbothioamides 2 with 2-bromoacetophenone. The structures of the newly synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, DEPT-135, and mass spectrometry analysis (MS). All new compounds were evaluated as antimicrobial and antioxidants. Compound (3b) exhibited moderate activity against Bacillus subtilis and Penicillium fimorum, 14 ± 0.5 mm and 18 ± 0.75 mm, respectively, while the other synthesized compounds did not show activity against the tested microbes. The most potent antioxidant activity showed by compound (2a) and (2e) with 95.2% and 96.3%, which considered good to excellent antioxidant activity compared with the control (ascorbic acid) and other synthesized compounds. Molecular docking study of the new compounds with cytochrome P450 14 alpha-sterol demethylase (CYP51) was carried out to evaluate their possibility as drugs and to implement structural improvements for this purpose. All synthesized compounds exhibited good affinity with (CYP51), notably, (3a) and (3b) compounds showed the highest affinity with the lowest binding energies.
Graphical abstract
中文翻译：
3-(2,5-dichlorothiophen-3-yl)-5-arylpyrazole-1-carbothioamides 及其噻唑衍生物的合成、表征、抗菌、抗氧化剂和分子对接研究
在本研究中，通过以下反应合成了一系列新的 3-(2,5-dichlorothiophen-3-yl)-5-aryl-4,5-dihydro-1 H -pyrazole-1-carbothioamides 2 E )-3-aryl-1-(2,5-dichlorothiophen-3-yl)prop-2-en-1-ones 1与氨基硫脲或通过 3-乙酰基-2,5-二氯噻吩与相应的醛和氨基硫脲。此外，2-(3-(2,5-dichlorothiophen-3-yl)-5-aryl-4,5-dihydro-1 H -pyrazol -1-yl)-4-phenylthiazoles 3的合成率为 46-89%通过用 2-溴苯乙酮回流碳硫代酰胺2得到。新合成化合物的结构通过IR、1 H-NMR、13 C-NMR、DEPT-135 和质谱分析 (MS)。所有新化合物都被评估为抗微生物剂和抗氧化剂。化合物( 3b)对枯草芽孢杆菌和纤毛青霉表现出中等活性，分别为14±0.5mm和18±0.75mm，而其他合成化合物对受试微生物没有表现出活性。化合物（ 2a）和（2e ）表现出最有效的抗氧化活性) 具有 95.2% 和 96.3%，与对照（抗坏血酸）和其他合成化合物相比，这被认为具有良好的抗氧化活性。对新化合物与细胞色素 P450 14 α-甾醇脱甲基酶 (CYP51) 进行分子对接研究，以评估它们作为药物的可能性，并为此目的进行结构改进。所有合成的化合物都表现出与（CYP51）的良好亲和力，特别是（3a）和（3b）化合物表现出最高的亲和力和最低的结合能。
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