Mohamed G. A. Mahmoud, Ahmed A. Fadda, Yasser A. Selim, Eslam R. El-Sawy, Sherihan A. El-Hadidy
{"title":"具有潜在抗菌活性的吡唑并[1,5-a]嘧啶衍生物的设计、合成和对接研究","authors":"Mohamed G. A. Mahmoud, Ahmed A. Fadda, Yasser A. Selim, Eslam R. El-Sawy, Sherihan A. El-Hadidy","doi":"10.1002/slct.202404260","DOIUrl":null,"url":null,"abstract":"<p>Compound 4,4′-(1,4-phenylenebis(thiazole-4,2-diyl))bis(1<i>H</i>-pyrazol-5-amine) <b>(5)</b> was used in the preparation of novel pyrazolo[1,5-a]pyrimidines incorporating a thiazole moiety (<b>6</b>, <b>7b</b>, <b>8</b>, <b>9</b>, and <b>13–18</b>). the reactions were described via the following reactions: acetylacetone, acetanilide, diethyl malonate, ethyl cyanoacetate, 3-(dimethylamino)-1-phenylprop-2-en-1-one, 2-((dimethylamino)methylene)-3-oxopentane-nitrile, 3-(dimethylamino)-1-(thiophen-3-yl)prop-2-en-1-one, 2-((dimethylamino)methylene)-5,5-dimethylcyclo-hexane-1,3-dione, dimethylformamide-dimethylacetal, and with a mixture of <i>p</i>-nitro benzaldehyde/cyclohexanone, respectively. Gram-positive bacteria <i>B. subtilis</i> and <i>B. thuringiensis</i>, as well as Gram-negative bacteria <i>E. coli</i> and <i>P. aeruginosa</i>, were tested for the newly synthesized compounds' in vitro antibacterial activity. Their in vitro antifungal activity against fungus strains <i>B. Fabae</i> and <i>F. oxysporum</i> was also assessed. The compounds <b>16–18</b> had the strongest activity against Gram-positive bacteria, with MIC values = 3.125 µg/mL against <i>B. subtilis</i>, which is equipotent to the drug reference Chloramphenicol, and MIC values = 6.25 µg/mL against <i>B. thuringiensis</i>, which is equipotent to the drug reference Cephalothin. Compounds (<b>13–18</b>) were shown to be superimposable to CNB based on their docking results, with the exception of derivative <b>18</b>. Furthermore, they demonstrated a strong binding mode with DNA gyrase B's active pocket (PDB: 1KZN) by forming several contacts with the enzyme's essential amino acids in a way that was comparable to CNB.</p>","PeriodicalId":146,"journal":{"name":"ChemistrySelect","volume":"9 43","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design, Synthesis, and Docking Study of Potentially Active Antimicrobial Pyrazolo[1,5-a]pyrimidine Derivatives\",\"authors\":\"Mohamed G. A. Mahmoud, Ahmed A. Fadda, Yasser A. Selim, Eslam R. El-Sawy, Sherihan A. 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Gram-positive bacteria <i>B. subtilis</i> and <i>B. thuringiensis</i>, as well as Gram-negative bacteria <i>E. coli</i> and <i>P. aeruginosa</i>, were tested for the newly synthesized compounds' in vitro antibacterial activity. Their in vitro antifungal activity against fungus strains <i>B. Fabae</i> and <i>F. oxysporum</i> was also assessed. The compounds <b>16–18</b> had the strongest activity against Gram-positive bacteria, with MIC values = 3.125 µg/mL against <i>B. subtilis</i>, which is equipotent to the drug reference Chloramphenicol, and MIC values = 6.25 µg/mL against <i>B. thuringiensis</i>, which is equipotent to the drug reference Cephalothin. Compounds (<b>13–18</b>) were shown to be superimposable to CNB based on their docking results, with the exception of derivative <b>18</b>. 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引用次数: 0
摘要
化合物 4,4′-(1,4-亚苯基双(噻唑-4,2-二基))双(1H-吡唑-5-胺)(5) 被用于制备含有噻唑分子的新型吡唑并[1,5-a]嘧啶(6、7b、8、9 和 13-18)。这些反应通过以下反应进行描述:乙酰丙酮、乙酰苯胺、丙二酸二乙酯、氰乙酸乙酯、3-(二甲基氨基)-1-苯基丙-2-烯-1-酮、2-((二甲基氨基)亚甲基)-3-氧代戊烷腈、3-(二甲基氨基)-1-(噻吩-3-基)丙-2-烯-1-酮、2-((二甲基氨基)亚甲基)-5,5-二甲基环己烷-1,3-二酮、二甲基甲酰胺-二甲基乙缩醛,以及对硝基苯甲醛/环己酮的混合物。对革兰氏阳性菌枯草杆菌和苏云金杆菌以及革兰氏阴性菌大肠杆菌和绿脓杆菌进行了体外抗菌活性测试。此外,还评估了它们对真菌菌株 B. Fabae 和 F. oxysporum 的体外抗真菌活性。化合物 16-18 对革兰氏阳性菌的活性最强,对枯草杆菌的 MIC 值为 3.125 µg/mL,与参考药物氯霉素相当;对苏云金杆菌的 MIC 值为 6.25 µg/mL,与参考药物头孢菌素相当。根据化合物(13-18)的对接结果,除衍生物 18 外,其他化合物均可与 CNB 叠加。此外,这些化合物与 DNA 回旋酶 B 的活性口袋(PDB:1KZN)有很强的结合模式,与该酶的必需氨基酸形成了多个接触点,其结合方式与 CNB 相当。
Design, Synthesis, and Docking Study of Potentially Active Antimicrobial Pyrazolo[1,5-a]pyrimidine Derivatives
Compound 4,4′-(1,4-phenylenebis(thiazole-4,2-diyl))bis(1H-pyrazol-5-amine) (5) was used in the preparation of novel pyrazolo[1,5-a]pyrimidines incorporating a thiazole moiety (6, 7b, 8, 9, and 13–18). the reactions were described via the following reactions: acetylacetone, acetanilide, diethyl malonate, ethyl cyanoacetate, 3-(dimethylamino)-1-phenylprop-2-en-1-one, 2-((dimethylamino)methylene)-3-oxopentane-nitrile, 3-(dimethylamino)-1-(thiophen-3-yl)prop-2-en-1-one, 2-((dimethylamino)methylene)-5,5-dimethylcyclo-hexane-1,3-dione, dimethylformamide-dimethylacetal, and with a mixture of p-nitro benzaldehyde/cyclohexanone, respectively. Gram-positive bacteria B. subtilis and B. thuringiensis, as well as Gram-negative bacteria E. coli and P. aeruginosa, were tested for the newly synthesized compounds' in vitro antibacterial activity. Their in vitro antifungal activity against fungus strains B. Fabae and F. oxysporum was also assessed. The compounds 16–18 had the strongest activity against Gram-positive bacteria, with MIC values = 3.125 µg/mL against B. subtilis, which is equipotent to the drug reference Chloramphenicol, and MIC values = 6.25 µg/mL against B. thuringiensis, which is equipotent to the drug reference Cephalothin. Compounds (13–18) were shown to be superimposable to CNB based on their docking results, with the exception of derivative 18. Furthermore, they demonstrated a strong binding mode with DNA gyrase B's active pocket (PDB: 1KZN) by forming several contacts with the enzyme's essential amino acids in a way that was comparable to CNB.
期刊介绍:
ChemistrySelect is the latest journal from ChemPubSoc Europe and Wiley-VCH. It offers researchers a quality society-owned journal in which to publish their work in all areas of chemistry. Manuscripts are evaluated by active researchers to ensure they add meaningfully to the scientific literature, and those accepted are processed quickly to ensure rapid online publication.