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一种氯乙酰胺衍生物,有望成为治疗镰孢菌病的候选药物。

A chloroacetamide derivative as a potent candidate for fusariosis treatment.

机构信息

Graduate Program in Agricultural Microbiology and Environment, Federal University of Rio Grande Do Sul, Sarmento Leite no 500 - Farroupilha, Porto Alegre, RS, 90050-170, Brazil.

Laboratório de Pesquisa Em Micologia Aplicada, Faculdade de Farmácia, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil.

出版信息

Braz J Microbiol. 2022 Sep;53(3):1289-1295. doi: 10.1007/s42770-022-00771-9. Epub 2022 Jun 1.

Abstract

Fusariosis has presented a significant increase in their incidence in the last years. This epidemiological panorama probably is due to the increasing profile of refractory susceptibility of Fusarium spp. to available drugs, especially in immunocompromised individuals. Thus, the development of new compounds with effectiveness on these organisms is a necessity. This study evaluated the antifungal potential of a chloroacetamide derivative (4-BFCA) against resistant Fusarium strains. As a result, the compound was effective against all strains (MIC range 12.5-50 μg/mL). The time kill assay demonstrated that 4-BFCA presents a concentration-dependent fungicidal action. Although its action mechanism has not yet been elucidated, it was possible to observe its efficacy through damages and alterations provoked along the hyphae of Fusarium spp. 4-BFCA maintained a high survival rate of Tenebrio molitor larvae, suggesting that it does not cause acute systemic toxicity on this host at the concentration evaluated. In addition, 4-BFCA was 83.33% effective in combating a fungal infection in vivo on the chorioallantoid membrane of embryonated eggs. Our results are very promising and arouse interest to investigate the action of 4-BFCA on Fusarium strains since it acts as a possible candidate for the development of new therapies for the treatment of fusariosis.

摘要

近年来,镰刀菌病的发病率显著增加。这种流行病学的情况可能是由于镰刀菌属对现有药物的耐药性不断增加,特别是在免疫功能低下的个体中。因此,开发对这些生物有效的新型化合物是必要的。本研究评估了一种氯乙酰胺衍生物(4-BFCA)对耐药性镰刀菌菌株的抗真菌潜力。结果表明,该化合物对所有菌株均有效(MIC 范围为 12.5-50μg/ml)。时间杀伤试验表明,4-BFCA 具有浓度依赖性杀菌作用。虽然其作用机制尚未阐明,但通过观察镰刀菌属菌丝的损伤和改变,可以观察到其功效。4-BFCA 对黄粉虫幼虫的存活率保持在较高水平,表明在评估浓度下,它不会对该宿主造成急性全身毒性。此外,4-BFCA 在体内对抗鸡胚绒毛尿囊膜上真菌感染的有效率为 83.33%。我们的研究结果非常有前途,引起了人们对 4-BFCA 对镰刀菌属作用的兴趣,因为它可能成为开发新的抗真菌疗法的候选药物。

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