Azoles containing naphthalene with activity against Gram-positive bacteria: in vitro studies and in silico predictions for flavohemoglobin inhibition.
J Biomol Struct Dyn
; 40(20): 10220-10229, 2022.
Article
en En
| MEDLINE
| ID: mdl-34139139
ABSTRACT
Azoles are first-line drugs used in fungal infections. Topical antifungals, such as miconazole and econazole, are known to be active against Gram-positive bacteria, which was reported to result from bacterial flavohemoglobin (flavoHb) inhibition. Dual antibacterial/antifungal action is believed to have benefits for antimicrobial chemotherapy. In this study, we tested antibacterial effects of an in-house library of naphthalene-bearing azoles, some of which were reported as potent antifungals, in an attempt to find dual-acting hits. Several potent derivatives were obtained against the Gram-positive bacteria, Enterococcus faecalis and Staphylococcus aureus. 9 was active at a minimum inhibitor concentration (MIC) less than 1 µg/ml against E. faecalis and S. aureus, and 10 against S. aureus. 16 was also potent against E. faecalis and S. aureus (MIC = 1 and 2 µg/ml, respectively). Six more were active against S. aureus with MIC ≤ 4 µg/ml. In vitro cytotoxicity studies showed that the active compounds were safe for healthy cells within their MIC ranges. According to the calculated descriptors, the library was found within the drug-like chemical space and free of pan-assay interference compounds (PAINS). Molecular docking studies suggested that the compounds might be bacterial flavohemoglobin (flavoHb) inhibitors and the azole and naphthalene rings were important pharmacophores, which was further supported by pharmacophore modeling study. As a result, the current study presents several non-toxic azole derivatives with antibacterial effects. In addition to their previously reported antifungal properties, they could set a promising starting point for the future design of dual acting antimicrobials. Communicated by Ramaswamy H. Sarma.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Staphylococcus aureus
/
Antiinfecciosos
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
J Biomol Struct Dyn
Año:
2022
Tipo del documento:
Article
País de afiliación:
Turquía