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新型黄酮并色烯部分化合物的合成、生物评估和构效关系研究。

Synthesis, Biological Assessment, and Structure Activity Relationship Studies of New Flavanones Embodying Chromene Moieties.

机构信息

Department of Chemistry, Taibah University, Madinah 30002, Saudi Arabia.

Department of Chemistry, University of Prince Edward Island, 550 University Avenue, Charlottetown, Prince Edward Island, PEI C1A 4P3, Canada.

出版信息

Molecules. 2020 Jan 27;25(3):544. doi: 10.3390/molecules25030544.

DOI:10.3390/molecules25030544
PMID:32012737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7037824/
Abstract

Novel flavanones that incorporate chromene motifs are synthesized via a one-step multicomponent reaction. The structures of the new chromenes are elucidated by using IR, H-NMR, C-NMR, H-H COSY, HSQC, HMBC, and elemental analysis. The new compounds are screened for their antimicrobial and cytotoxic activities. The antimicrobial properties are investigated and established against seven human pathogens, employing the agar well diffusion method and the minimum inhibitory concentrations. A majority of the assessed derivatives are found to exhibit significant antimicrobial activities against most bacterial strains, in comparison to standard reference drugs. Moreover, their cytotoxicity is appraised against four different human carcinoma cell lines: human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), human breast adenocarcinoma (MCF-7), and adenocarcinoma human alveolar basal epithelial cell (A-549). All the desired compounds are subjected to studies, forecasting their drug likeness, bioactivity, and the absorption, distribution, metabolism, and excretion (ADME) properties prior to their synthetic assembly. The molecular docking evaluation of all the targeted derivatives is undertaken on gyrase B and the cyclin-dependent kinase. The predicted outcomes were endorsed by the studies.

摘要

通过一步多组分反应合成了含有色烯基的新型黄烷酮。利用 IR、H-NMR、C-NMR、H-H COSY、HSQC、HMBC 和元素分析阐明了新色烯的结构。对新化合物进行了抗菌和细胞毒性活性筛选。采用琼脂孔扩散法和最小抑菌浓度法,对七种人体病原体进行了抗菌特性研究和建立。与标准参考药物相比,评估的大多数衍生化合物对大多数细菌菌株表现出显著的抗菌活性。此外,还针对四种不同的人癌细胞系(人结肠癌细胞(HCT-116)、人肝癌细胞(HepG-2)、人乳腺癌腺癌细胞(MCF-7)和人肺泡基底上皮细胞腺癌细胞(A-549))评估了它们的细胞毒性。在进行合成组装之前,对所有目标化合物进行了药物相似性、生物活性以及吸收、分布、代谢和排泄(ADME)特性的研究。对所有靶向衍生物进行了拓扑异构酶 B 和细胞周期蛋白依赖性激酶的分子对接评估。预测结果得到了研究的支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/419069d08610/molecules-25-00544-g012a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/a7f5a6878d8c/molecules-25-00544-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/18da17c587a2/molecules-25-00544-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/802a70a0f78c/molecules-25-00544-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/94fedba54c47/molecules-25-00544-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/dc326e7d297e/molecules-25-00544-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/632893a6df82/molecules-25-00544-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/ca822b4a55cd/molecules-25-00544-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/9b0088394a90/molecules-25-00544-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/2c5019cdb9a3/molecules-25-00544-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/034ccc2f820c/molecules-25-00544-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/55b7634940cd/molecules-25-00544-g009a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/5efaefa2c075/molecules-25-00544-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/745217666cfb/molecules-25-00544-g011a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/419069d08610/molecules-25-00544-g012a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/a7f5a6878d8c/molecules-25-00544-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/18da17c587a2/molecules-25-00544-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/802a70a0f78c/molecules-25-00544-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/94fedba54c47/molecules-25-00544-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/dc326e7d297e/molecules-25-00544-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/632893a6df82/molecules-25-00544-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/ca822b4a55cd/molecules-25-00544-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/9b0088394a90/molecules-25-00544-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/2c5019cdb9a3/molecules-25-00544-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/034ccc2f820c/molecules-25-00544-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/55b7634940cd/molecules-25-00544-g009a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/5efaefa2c075/molecules-25-00544-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/745217666cfb/molecules-25-00544-g011a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca20/7037824/419069d08610/molecules-25-00544-g012a.jpg

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