Synthesis, Antimicrobial, Anti-Virulence and Anticancer Evaluation of New 5(4H)-Oxazolone-Based Sulfonamides.
Synthesis, Antimicrobial, Anti-Virulence and Anticancer Evaluation of New 5(4H)-Oxazolone-Based Sulfonamides.
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DOI：
10.3390/molecules27030671
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发表时间：
2022-01-20
期刊：
影响因子：
--
通讯作者：
Al-Mahmoudy AMM
中科院分区：
文献类型：
--
作者：
Almalki AJ;Ibrahim TS;Taher ES;Mohamed MFA;Youns M;Hegazy WAH;Al-Mahmoudy AMM
由于第一个前药prontosil的合成共享其化学部分，磺胺类药物表现出多种作用模式，可用作抗菌剂、利尿剂、抗糖尿病剂和其他临床应用。这个鼓舞人心的化学核心促进了几个研究小组研究新成员的合成，探索新的临床应用。本研究合成了一系列新型的5（4 H）-恶唑酮磺酰胺类化合物（OBS）9a-k，并对它们对革兰氏阳性菌和革兰氏阴性菌及真菌的抗菌和抗真菌活性进行了评价。大多数测试的化合物对革兰氏阳性和阴性细菌都表现出有希望的抗菌活性，特别是OBS 9 b和9 f。其中化合物9 h的抗真菌活性最强。此外，对在最低浓度下抑制细菌生长的OBS 9a、9 b和9 f进行针对铜绿假单胞菌和金黄色葡萄球菌的抗毒力活性的进一步评价。有趣的是，三种测试化合物减少了铜绿假单胞菌和沙门氏菌中生物膜的形成并减少了毒力因子的产生。金黄色。细菌使用一个信号系统，群体感应（QS），来调节它们的毒力。在这种情况下，进行了计算机模拟研究，以评估OBS与QS受体竞争的能力。所测试的OBS显示出显著的结合和阻碍QS受体的能力，表明OBS的抗毒力活性可能是由于阻断QS，即控制细菌毒力的系统。此外，已经进一步对这些衍生物进行了抗癌活性研究。OBS化合物针对不同的癌细胞系显示出不同的抗肿瘤活性，特别是9a、9 b、9 f和9 k。因此，OBS化合物可作为抗菌剂、抗病毒剂和抗肿瘤剂。
Since the synthesis of prontosil the first prodrug shares their chemical moiety, sulfonamides exhibit diverse modes of actions to serve as antimicrobials, diuretics, antidiabetics, and other clinical applications. This inspiring chemical nucleus has promoted several research groups to investigate the synthesis of new members exploring new clinical applications. In this study, a novel series of 5(4H)-oxazolone-based-sulfonamides (OBS) 9a–k were synthesized, and their antibacterial and antifungal activities were evaluated against a wide range of Gram-positive and -negative bacteria and fungi. Most of the tested compounds exhibited promising antibacterial activity against both Gram-positive and -negative bacteria particularly OBS 9b and 9f. Meanwhile, compound 9h showed the most potent antifungal activity. Moreover, the OBS 9a, 9b, and 9f that inhibited the bacterial growth at the lowest concentrations were subjected to further evaluation for their anti-virulence activities against Pseudomonas aeruginosa and Staphylococcus aureus. Interestingly, the three tested compounds reduced the biofilm formation and diminished the production of virulence factors in both P. aeruginosa and S. aureus. Bacteria use a signaling system, quorum sensing (QS), to regulate their virulence. In this context, in silico study has been conducted to assess the ability of OBS to compete with the QS receptors. The tested OBS showed marked ability to bind and hinder QS receptors, indicating that anti-virulence activities of OBS could be due to blocking QS, the system that controls the bacterial virulence. Furthermore, anticancer activity has been further performed for such derivatives. The OBS compounds showed variable anti-tumor activities, specifically 9a, 9b, 9f and 9k, against different cancer lines. Conclusively, the OBS compounds can serve as antimicrobials, anti-virulence and anti-tumor agents.
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DOI：
10.3390/antibiotics10010025
发表时间：
2020-12-30
期刊：
Antibiotics (Basel, Switzerland)
影响因子：
--
作者：
Bendary MM;Ibrahim D;Mosbah RA;Mosallam F;Hegazy WAH;Awad NFS;Alshareef WA;Alomar SY;Zaitone SA;Abd El-Hamid MI
通讯作者：
Abd El-Hamid MI
DOI：
10.3390/antibiotics9100667
发表时间：
2020-10-03
期刊：
Antibiotics (Basel, Switzerland)
影响因子：
--
作者：
Abd El-Hamid MI;Y El-Naenaeey ES;M Kandeel T;Hegazy WAH;Mosbah RA;Nassar MS;Bakhrebah MA;Abdulaal WH;Alhakamy NA;Bendary MM
通讯作者：
Bendary MM
影响因子：
3.4
作者：
Ballatore, Carlo;Huryn, Donna M.;Smith, Amos B., III
通讯作者：
Smith, Amos B., III
DOI：
10.3109/14756366.2016.1160077
发表时间：
2016-01-01
影响因子：
5.6
作者：
Gul, Halise Inci;Tugrak, Mehtap;Supuran, Claudiu T.
通讯作者：
Supuran, Claudiu T.
影响因子：
3.8
作者：
Askoura, Momen;Youns, Mahmoud;Hegazy, Wael Abdel Halim
通讯作者：
Hegazy, Wael Abdel Halim