School of Pharmacy and Pharmacology, Griffith University, Gold Coast, QLD 4222, Australia.
School of Pharmacy and Pharmacology, Griffith University, Gold Coast, QLD 4222, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD 4222, Australia.
Bioorg Med Chem Lett. 2021 May 1;39:127853. doi: 10.1016/j.bmcl.2021.127853. Epub 2021 Feb 18.
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a significant burden both clinically and economically worldwide. Increasing resistance to current antibiotics requires an urgent investigation into novel classes of antimicrobial agents. This study presents a structure-activity relationship (SAR) rationale for pyrazole linked phenylthiazole analogues as new antibacterial agents. A library of 23 novel pyrazole linked phenylthiazole compounds were synthesised, followed by screening for antimicrobial activity against five bacterial species and two fungi. The most active compound 14b has shown promising antibacterial activity against the Gram-positive methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300) strain (MIC 4 μg/mL). Furthermore, the active pyrazole linked phenylthiazole compound exhibited a better toxicity profile than standard antibiotics. In summary, these results demonstrate that a pyrazole linked phenylthiazole scaffold has potential as a lead for further investigation to afford novel antibacterial agents.
耐甲氧西林金黄色葡萄球菌（MRSA）感染在全球范围内无论在临床还是经济方面均造成了沉重负担。目前抗生素耐药性不断增加，迫切需要对新型抗菌药物进行研究。本研究提出了将吡唑连接苯并噻唑类似物作为新型抗菌剂的结构-活性关系（SAR）依据。合成了 23 种新型吡唑连接苯并噻唑化合物库，然后对其针对五种细菌和两种真菌的抗菌活性进行筛选。最活跃的化合物 14b 对革兰氏阳性耐甲氧西林金黄色葡萄球菌（MRSA，ATCC 43300 株）（MIC 4μg/mL）表现出有前景的抗菌活性。此外，活性吡唑连接苯并噻唑化合物表现出比标准抗生素更好的毒性特征。总之，这些结果表明，吡唑连接苯并噻唑骨架具有作为进一步研究新型抗菌剂的潜在用途。
