Shoaib Khan, Rafaqat Hussain, Yousaf Khan, Tayyiaba Iqbal, Saeed Anwar, Tariq Aziz, Metab Alharbi
{"title":"基于体外酶法、硅学 ADME 和分子对接分析鉴定新型双吲哚含三嗪-噻唑杂环衍生物作为有前景的脲酶抑制剂","authors":"Shoaib Khan, Rafaqat Hussain, Yousaf Khan, Tayyiaba Iqbal, Saeed Anwar, Tariq Aziz, Metab Alharbi","doi":"10.1515/znc-2024-0061","DOIUrl":null,"url":null,"abstract":"The current study details a sequence of sequential reactions for synthesizing bis-indole-based triazine bearing thiazole derivatives. Several steps were involved in the synthesis of bis-indole-based triazine bearing thiazole derivative. The synthetic reactions were monitored via thin-layer chromatography (TLC). Synthesized compounds were characterized using various spectroscopic techniques, including <jats:sup>1</jats:sup>H NMR, <jats:sup>13</jats:sup>C NMR, and HR-EIMS. The inhibitory activity against urease enzyme of these synthesized compounds was compared with that of thiourea, a standard drug (IC<jats:sub>50</jats:sub> = 9.30 ± 0.20 µM). A range of inhibitory potencies were observed for the synthesized compounds, ranging from moderate to excellent, as follows (IC<jats:sub>50</jats:sub> = 5.10 ± 0.40 µM to 29.80 ± 0.20 µM). Analyzing the structure–activity relationship (SAR) provided insight into the results, showing that different substituents had different effects on aromatic rings. Several compounds displayed outstanding inhibitory properties (among those tested were 1, 2, 4, 5, and 6 with IC<jats:sub>50</jats:sub> = 6.30 ± 0.80, 5.10 ± 0.40, 5.90 ± 0.50, 8.20 ± 0.10, 8.90 ± 0.60 µM, respectively). Anti-urease evaluation of all the synthesized derivatives was conducted in which the selected compounds have shown remarkable potency compared with the standard drug thiourea (IC<jats:sub>50</jats:sub> = 9.30 ± 0.20 µM). Molecular docking analysis was carried out for investigating the better binding sites and distance of the derivatives. Moreover, the drug-like properties were explored by the ADME attributes of the synthesized analogs.","PeriodicalId":23894,"journal":{"name":"Zeitschrift für Naturforschung C","volume":"118 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In vitro enzymatic, in silico ADME and molecular docking based analysis for the identification of novel bis-indole containing triazine–thiazole hybrids derivatives as promising urease inhibitors\",\"authors\":\"Shoaib Khan, Rafaqat Hussain, Yousaf Khan, Tayyiaba Iqbal, Saeed Anwar, Tariq Aziz, Metab Alharbi\",\"doi\":\"10.1515/znc-2024-0061\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The current study details a sequence of sequential reactions for synthesizing bis-indole-based triazine bearing thiazole derivatives. Several steps were involved in the synthesis of bis-indole-based triazine bearing thiazole derivative. The synthetic reactions were monitored via thin-layer chromatography (TLC). Synthesized compounds were characterized using various spectroscopic techniques, including <jats:sup>1</jats:sup>H NMR, <jats:sup>13</jats:sup>C NMR, and HR-EIMS. The inhibitory activity against urease enzyme of these synthesized compounds was compared with that of thiourea, a standard drug (IC<jats:sub>50</jats:sub> = 9.30 ± 0.20 µM). A range of inhibitory potencies were observed for the synthesized compounds, ranging from moderate to excellent, as follows (IC<jats:sub>50</jats:sub> = 5.10 ± 0.40 µM to 29.80 ± 0.20 µM). Analyzing the structure–activity relationship (SAR) provided insight into the results, showing that different substituents had different effects on aromatic rings. Several compounds displayed outstanding inhibitory properties (among those tested were 1, 2, 4, 5, and 6 with IC<jats:sub>50</jats:sub> = 6.30 ± 0.80, 5.10 ± 0.40, 5.90 ± 0.50, 8.20 ± 0.10, 8.90 ± 0.60 µM, respectively). Anti-urease evaluation of all the synthesized derivatives was conducted in which the selected compounds have shown remarkable potency compared with the standard drug thiourea (IC<jats:sub>50</jats:sub> = 9.30 ± 0.20 µM). Molecular docking analysis was carried out for investigating the better binding sites and distance of the derivatives. Moreover, the drug-like properties were explored by the ADME attributes of the synthesized analogs.\",\"PeriodicalId\":23894,\"journal\":{\"name\":\"Zeitschrift für Naturforschung C\",\"volume\":\"118 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-04-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Zeitschrift für Naturforschung C\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1515/znc-2024-0061\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Zeitschrift für Naturforschung C","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/znc-2024-0061","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
In vitro enzymatic, in silico ADME and molecular docking based analysis for the identification of novel bis-indole containing triazine–thiazole hybrids derivatives as promising urease inhibitors
The current study details a sequence of sequential reactions for synthesizing bis-indole-based triazine bearing thiazole derivatives. Several steps were involved in the synthesis of bis-indole-based triazine bearing thiazole derivative. The synthetic reactions were monitored via thin-layer chromatography (TLC). Synthesized compounds were characterized using various spectroscopic techniques, including 1H NMR, 13C NMR, and HR-EIMS. The inhibitory activity against urease enzyme of these synthesized compounds was compared with that of thiourea, a standard drug (IC50 = 9.30 ± 0.20 µM). A range of inhibitory potencies were observed for the synthesized compounds, ranging from moderate to excellent, as follows (IC50 = 5.10 ± 0.40 µM to 29.80 ± 0.20 µM). Analyzing the structure–activity relationship (SAR) provided insight into the results, showing that different substituents had different effects on aromatic rings. Several compounds displayed outstanding inhibitory properties (among those tested were 1, 2, 4, 5, and 6 with IC50 = 6.30 ± 0.80, 5.10 ± 0.40, 5.90 ± 0.50, 8.20 ± 0.10, 8.90 ± 0.60 µM, respectively). Anti-urease evaluation of all the synthesized derivatives was conducted in which the selected compounds have shown remarkable potency compared with the standard drug thiourea (IC50 = 9.30 ± 0.20 µM). Molecular docking analysis was carried out for investigating the better binding sites and distance of the derivatives. Moreover, the drug-like properties were explored by the ADME attributes of the synthesized analogs.