Pereira Antônio Mateus Gomes, da Silva Benise Ferreira, Araujo Ingrid Maria Frota, Aguiar Francisco Kauê Carvalho, Coelho Paulo Adenes Teixeira, Costa Renata Albuquerque, Marinho Marcia Machado, Marinho Emmanuel Silva, Nunes João Victor Serra, Carneiro Victor Alves, Santos Hélcio Silva Dos
Graduate Program in Biotechnology, Northeast Network of Biotechnology (RENORBIO), State University of Ceará, Campus Itaperi, Fortaleza 60714-903, Brazil.
Center of Bioprospection and Experimentation Molecular Applied (NUBEM), University Center INTA-UNINTA, Sobral 62050-100, Brazil.
Antibiotics (Basel). 2025 Mar 10;14(3):286. doi: 10.3390/antibiotics14030286.
The rise of multidrug-resistant (MDR) bacteria poses a significant challenge to global public health, contributing to increased morbidity and mortality rates. In this context, the repurposing of existing drugs has emerged as a promising strategy. In this study, hydralazine (HDZ), a vasodilator used as an antihypertensive since 1952, demonstrated antibacterial and antibiofilm activity against both Gram-positive and Gram-negative bacteria. In this study, the antibacterial activity of the antihypertensive hydralazine (HDZ) was evaluated against Gram-positive and Gram-negative strains through minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), growth curve with MIC and sub-MIC doses, combinatorial effect with gentamicin, scanning electron microscopy (SEM), molecular docking, and antibiofilm activity. The MIC and MBC values ranged from 39.5 to 1.250 μg/mL, respectively. A change in the growth kinetics of the strains was observed when exposed to MIC and 1/2 MIC values, with a delay in the phases of up to 12 h. The combinatorial effect with gentamicin demonstrated an additive and indifferent potential when combined with HDZ. Furthermore, hydralazine showed antibiofilm activity against the tested strains, including MRSA. Electron microscopy analysis revealed significant changes in bacterial morphology when exposed to the MIC dose of HDZ for 4 h. The overall results of the study indicate hydralazine as a potential agent in the fight against bacterial infections.
多重耐药（MDR）细菌的出现对全球公共卫生构成了重大挑战，导致发病率和死亡率上升。在此背景下，现有药物的重新利用已成为一种有前景的策略。在本研究中，肼屈嗪（HDZ）自1952年起用作抗高血压药的血管扩张剂，对革兰氏阳性和革兰氏阴性细菌均表现出抗菌和抗生物膜活性。在本研究中，通过最低抑菌浓度（MIC）、最低杀菌浓度（MBC）、MIC和亚MIC剂量的生长曲线、与庆大霉素的联合效应、扫描电子显微镜（SEM）、分子对接以及抗生物膜活性，评估了抗高血压药肼屈嗪（HDZ）对革兰氏阳性和革兰氏阴性菌株的抗菌活性。MIC和MBC值分别为39.5至1250μg/mL。当暴露于MIC和1/2 MIC值时，观察到菌株生长动力学发生变化，生长阶段延迟长达12小时。与庆大霉素的联合效应表明与HDZ联合时具有相加和无关的潜力。此外，肼屈嗪对包括耐甲氧西林金黄色葡萄球菌（MRSA）在内的受试菌株表现出抗生物膜活性。电子显微镜分析显示，当暴露于HDZ的MIC剂量4小时时，细菌形态发生了显著变化。该研究的总体结果表明，肼屈嗪是对抗细菌感染的潜在药物。
