Monteiro Kadja Luana Chagas, Silva Osmar Nascimento, Dos Santos Nascimento Igor José, Mendonça Júnior Francisco Jaime Bezerra, Aquino Pedro Gregório Vieira, da Silva-Júnior Edeildo Ferreira, de Aquino Thiago Mendonça
Research Group on Therapeutic Strategies - GPET, Laboratory of Synthesis and Research in Medicinal Chemistry - LSPMED, Institute of Chemistry and Biotechnology, Federal University of Alagoas, 57072-970, Maceió, Alagoas, Brazil.
Faculty of Pharmacy, University Center of Anápolis, Unievangélica, 75083-515, Anápolis, Goiás, Brazil.
Curr Top Med Chem. 2022;22(24):1983-2028. doi: 10.2174/1568026622666220321124452.
The discovery of antibiotics was a revolutionary feat that provided countless health benefits. The identification of penicillin by Alexander Fleming initiated the era of antibiotics, represented by constant discoveries that enabled effective treatments for the different classes of diseases caused by bacteria. However, the indiscriminate use of these drugs allowed the emergence of resistance mechanisms of these microorganisms against the available drugs. In addition, the constant discoveries in the 20th century generated a shortage of new molecules, worrying health agencies and professionals about the appearance of multidrug-resistant strains against available drugs. In this context, the advances of recent years in molecular biology and microbiology have allowed new perspectives in drug design and development, using the findings related to the mechanisms of bacterial resistance to generate new drugs that are not affected by such mechanisms and supply new molecules to be used to treat resistant bacterial infections. Besides, a promising strategy against bacterial resistance is the combination of drugs through adjuvants, providing new expectations in designing new antibiotics and new antimicrobial therapies. Thus, this manuscript will address the main mechanisms of bacterial resistance under the understanding of medicinal chemistry, showing the main active compounds against efflux mechanisms, and also the application of the use of drug delivery systems, and finally, the main potential natural products as adjuvants or with promising activity against resistant strains.
抗生素的发现是一项具有变革性的壮举，带来了无数的健康益处。亚历山大·弗莱明发现青霉素开启了抗生素时代，此后不断有新发现，使得针对各类由细菌引起的疾病能够进行有效治疗。然而，这些药物的滥用导致这些微生物对现有药物产生了耐药机制。此外，20世纪的持续发现造成了新分子的短缺，这让卫生机构和专业人士担心会出现对现有药物具有多重耐药性的菌株。在这种背景下，近年来分子生物学和微生物学的进展为药物设计和开发带来了新的视角，利用与细菌耐药机制相关的研究结果来开发不受此类机制影响的新药，并提供用于治疗耐药细菌感染的新分子。此外，一种有前景的对抗细菌耐药性的策略是通过佐剂进行药物联合，这为设计新型抗生素和新型抗菌疗法带来了新的希望。因此，本手稿将在药物化学的理解框架下阐述细菌耐药的主要机制，展示针对外排机制的主要活性化合物，以及药物递送系统的应用，最后介绍作为佐剂或对耐药菌株具有潜在活性的主要天然产物。
