Catalano Alessia, Iacopetta Domenico, Pellegrino Michele, Aquaro Stefano, Franchini Carlo, Sinicropi Maria Stefania
Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, 70126 Bari, Italy.
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy.
Antibiotics (Basel). 2021 Jan 19;10(1):92. doi: 10.3390/antibiotics10010092.
Antimicrobials have allowed medical advancements over several decades. However, the continuous emergence of antimicrobial resistance restricts efficacy in treating infectious diseases. In this context, the drug repositioning of already known biological active compounds to antimicrobials could represent a useful strategy. In 2002 and 2003, the SARS-CoV pandemic immobilized the Far East regions. However, the drug discovery attempts to study the virus have stopped after the crisis declined. Today's COVID-19 pandemic could probably have been avoided if those efforts against SARS-CoV had continued. Recently, a new coronavirus variant was identified in the UK. Because of this, the search for safe and potent antimicrobials and antivirals is urgent. Apart from antiviral treatment for severe cases of COVID-19, many patients with mild disease without pneumonia or moderate disease with pneumonia have received different classes of antibiotics. Diarylureas are tyrosine kinase inhibitors well known in the art as anticancer agents, which might be useful tools for a reposition as antimicrobials. The first to come onto the market as anticancer was sorafenib, followed by some other active molecules. For this interesting class of organic compounds antimicrobial, antiviral, antithrombotic, antimalarial, and anti-inflammatory properties have been reported in the literature. These numerous properties make these compounds interesting for a new possible pandemic considering that, as well as for other viral infections also for CoVID-19, a multitarget therapeutic strategy could be favorable. This review is meant to be an overview on diarylureas, focusing on their biological activities, not dwelling on the already known antitumor activity. Quite a lot of papers present in the literature underline and highlight the importance of these molecules as versatile scaffolds for the development of new and promising antimicrobials and multitarget agents against new pandemic events.
几十年来，抗菌药物推动了医学进步。然而，抗菌药物耐药性的不断出现限制了治疗传染病的疗效。在这种背景下，将已知生物活性化合物重新定位为抗菌药物可能是一种有用的策略。2002年和2003年，严重急性呼吸综合征冠状病毒（SARS-CoV）大流行使远东地区陷入停滞。然而，在危机消退后，针对该病毒的药物研发尝试停止了。如果当时针对SARS-CoV的努力持续下去，如今的新冠疫情或许本可避免。最近，在英国发现了一种新型冠状病毒变种。因此，迫切需要寻找安全有效的抗菌药物和抗病毒药物。除了对新冠肺炎重症病例进行抗病毒治疗外，许多轻症无肺炎或中症有肺炎的患者也接受了不同种类的抗生素治疗。二芳基脲是本领域熟知的作为抗癌剂的酪氨酸激酶抑制剂，可能是重新定位为抗菌药物的有用工具。作为抗癌药物最早上市的是索拉非尼，随后还有其他一些活性分子。对于这类有趣的有机化合物，文献中已报道了其具有抗菌、抗病毒、抗血栓、抗疟疾和抗炎特性。考虑到对于新冠病毒以及其他病毒感染，多靶点治疗策略可能是有利的，这些众多特性使得这些化合物对于应对新的大流行具有吸引力。本综述旨在对二芳基脲进行概述，重点关注其生物活性，而非详述其已知的抗肿瘤活性。文献中相当多的论文强调并突出了这些分子作为开发新型且有前景的抗菌药物和针对新的大流行事件的多靶点药物的通用骨架的重要性。
