Synthesis and anti Methicillin resistant Staphylococcus aureus activity of substituted chalcones alone and in combination with non-beta-lactam antibiotics.
A total of 30 chalcone analogues was synthesized via a base catalyzed Claisen Schmidt condensation and screened for their in vitro antibacterial activity against Methicillin-sensitive Staphylococcus aureus (MSSA) and Methicillin-resistant Staphylococcus aureus (MRSA) alone or in combination with non beta-lactam antibiotics namely ciprofloxacin, chloramphenicol, erythromycin, vancomycin, doxycycline and gentamicin. In the checkerboard technique, fractional inhibitory concentration indices (FICI) show that the following combinations like ciprofloxacin with 25 (4'-bromo-2-hydroxychalcone); doxycycline with 21 (4-hydroxychalcone); doxycycline with 25; and doxycycline with 4 (2',2-dihydroxychalcone) were synergistic against MRSA. In term SAR study, the relationship between chalcone structure and their antibacterial activity against S. aureus and synergy with tested antibiotics were discussed. Possible mechanisms for antibacterial activity of chalcones alone as well as the synergistic effect in combinations were proposed by molecular modeling studies, respectively. Combinations of chalcones with conventional antibiotics could be an effective alternative in the treatment of infection caused by MRSA.
Department of Medicinal Chemistry, School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, 41 Dinh Tien Hoang, Dist. 1, Ho Chi Minh City, Viet Nam. tranthanhdao@uphcm.edu.vn
Thanh-Dao
TD
Tran
Tuong-Ha
TH
Do
Ngoc-Chau
NC
Tran
Trieu-Du
TD
Ngo
Thi-Ngoc-Phuong
TN
Huynh
Cat-Dong
CD
Tran
Khac-Minh
KM
Thai
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D047090:beta-Lactams