Affiliation:
1. Department of Organic and Inorganic Chemistry Science Center Federal University of Ceará Fortaleza CE 60455-760 Brazil
2. Institute of Exact and Natural Sciences University of International Integration of Afro-Brazilian Lusofonia 62785-000 Acarape CE Brazil
3. Embrapa Tropical Agroindustry 60511-110 Fortaleza Ceará Brazil
4. Department of Physiology and Pharmacology Federal University of Ceará 60165-085 Fortaleza Ceará Brazil
5. Integrated Laboratory of Biomolecules (LIBS) Department of Pathology and Legal Medicine Federal University of Ceará Fortaleza CE 62042-280 Brazil
6. Faculty of Education of Itapipoca (FACEDI) State University of Ceará Itapipoca CE 62500-000 Brazil
Abstract
AbstractThe crude acetone extract of a marine Micromonospora sp. strain associated with Eudistoma vannnamei was fractioned with hexane and ethyl acetate. The crude extract and both soluble fractions were assayed against several bacteria strains. The new polycyclic quinones 12‐hydroxy‐9‐propyltetracene‐6,1‐dione (1), 5,12‐dihydroxy‐4‐methoxy‐9‐propyltetracene‐5,12‐dione (2), and 4,6‐dihydroxy‐3‐methoxycarbonyl‐ methyl‐6a‐(oxobutyl)‐5,12‐anthraquinone (3), along with the known 4,6‐dihydroxy‐3‐methoxycarbonyl‐methyl‐6a‐(oxo‐3‐methyl‐butyl)‐5,12‐anthraquinone (4) and 4,6‐dihydroxy‐3‐methoxycarbonyl‐methyl‐6a‐(oxopentyl)‐5,12‐anthraquinone (5) were isolated from the hexane‐soluble fraction, while from the active ethyl acetate fraction were isolated the known 4,6,11‐trihydroxy‐9‐propyltetracene‐5,12‐dione (6), 4‐methoxy‐9‐propyltetracene‐6,11‐dione (7), 7,8,9,10‐tetrahydro‐9‐hydroxy‐4‐methoxy‐9‐propyltetracene‐6,11‐dione (8), and 10β‐carbomethoxy‐7,8,9,10‐tetrahydro‐4,6,7α,9α,11‐pentahydroxy‐9‐propyltetracene‐5,12‐dione (9). The structures of the new compounds were established by interpretation of HRMS and NMR techniques. A study of molecular docking was performed with the compounds from the active ethyl acetate fraction to correlate tentatively with the antimicrobial activity. Molecular docking, RMSD, RMSF, and MM‐GBSA evaluations were performed to investigate the inhibitory activity of 6–8 against the protein PDB‐codex 1MWT, being considered a promising target for studying drug development responsible for inhibiting replication of Staphylococcus aureus. Penicillin G was used as the standard inhibitory. Anthracyclinones 6–8 were the best hydrolase inhibitor with affinity energy −8.1 to −7.9 kcal/mol compared to penicillin G, which presented −6.9 kcal/mol. Both 8 and 7 present potent inhibitory effects against hydrolase through molecular dynamics simulation and exhibit favorable drug‐like properties, promising new hydrolase blockers to fight bacterial infections from Staphylococcus aureus.