RESUMEN
A series of new imidazole-phenazine derivatives were synthesized via a two-step process. The condensation of 2,3-diaminophenazine and benzaldehyde derivatives proceeds with intermediate formation of an aniline Schiff base, which undergoes subsequent cyclodehydrogenation in situ. The structures of the synthesized compounds were characterized by 1D and 2D NMR, FTIR and HRMS. A total of thirteen imidazole phenazine derivatives were synthesized and validated for their inhibitory activity as anti-dengue agents by an in vitro DENV2 NS2B-NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Two para-substituted imidazole phenazines, 3e and 3k, were found to be promising lead molecules for novel NS2B-NS3 protease inhibitors with IC50 of 54.8 µM and 71.9 µM, respectively, compared to quercetin as a control (IC50 104.8 µM). The in silico study was performed using AutoDock Vina to identify the binding energy and conformation of 3e and 3k with the active site of the DENV2 NS2B-NS3 protease Wichapong model. The results indicate better binding properties of 3e and 3k with calculated binding energies of -8.5 and -8.4 kcal mol-1, respectively, compared to the binding energy of quercetin of -7.2 kcal mol-1, which corroborates well with the experimental observations.
RESUMEN
Alpinia conchigera Griff. is a plant species from the family Zingiberaceae. Coloquially known as wild ginger, Alpinia conchigera Griff. is used as food condiment and for traditional treatment of skin diseases. Isolation studies to identify bioactive compounds of rhizomes of Alpinia conchigera yielded seven compounds; 1'S-1'-acetoxychavicol acetate (1), trans-p-coumaryl diacetate (2), p-hydroxycinnamyl acetate (3), 1'S-1'-hydroxychavicol acetate (4) p-hydroxybenzaldehyde (5), stigmasterol (6) and ß-sitosterol (7). Compounds 1, 2 and 5 were evaluated for antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). Among the compounds tested, Compound 1 showed good antimicrobial activity against the strain of MRSA with minimum inhibition concentration (MIC) value of 0.5 mg/mL. Meanwhile, Compounds 2 and 5 exhibited moderate activity with MIC value between 1.0 and 2.0 mg/mL. These findings indicate antimicrobial potential of 1'S-1'-acetoxychavicol acetate (1), compound derived from rhizome of Alpinia conchigera Griff. against MRSA, which warrant further investigation.
RESUMEN
Aims@#This study aimed to evaluate the antimicrobial activity of naturally derived phenylpropanoids from Alpinia conchigera (A. conchigera) Griff. and its synthetic analogues, as well as interactions between selected compounds with first-line tuberculosis (TB) drug, rifampicin, against Mycobacterium smegmatis, a potential opportunistic nontuberculous mycobacterium (NTM) and a surrogate organism for TB. @*Methodology and results@#Twelve phenylpropanoids of A. conchigera were evaluated for antimicrobial activity against M. smegmatis (ATCC 14468). The phenylpropanoid compound from A. conchigera with the lowest minimum inhibitory concentration and bactericidal (MIC, MBC) values were selected for checkerboard tetrazolium microplate assay (TEMA) with rifampicin to determine drug interactions. A majority of the compounds had antimicrobial activity, however, purified natural compound 1'S-1'-acetoxychavicol acetate (ACA) showed the highest antimicrobial activity with an MIC value of 62.5 µg/mL against M. smegmatis. The combination of ACA and rifampicin produced indifferent interaction with fractional inhibition concentration (FIC) index of 1.5, while the combination of rifampicin and ACA synthetic analogue 4-allyl-2,6- methoxyphenyl isobutyrate produced a synergistic interaction effect with FIC index of 0.5. None of the compounds tested were bactericidal but appear to be bacteriostatic.@*Conclusion, significance and impact of study@#This study presents the first report on the antimicrobial potential of natural A. conchigera-derived ACA against M. smegmatis as well as the synergistic interaction of 4-allyl-2,6- methoxyphenyl isobutyrate with rifampicin which warrants further investigation.