RESUMO
This systematic review aims to evaluate the antimicrobial activity of α-mangostin derived from Garcinia mangostana against different microbes. A literature search was performed using PubMed and Science Direct until March 2022. The research question was developed based on a PICO (Population, Intervention, Control and Outcomes) model. In this study, the population of interest was microbes, α-mangostin extracted from Garcinia mangostana was used as exposure while antibiotics were used as control, followed by the outcome which is determined by the antimicrobial activity of α-mangostin against studied microbes. Two reviewers independently performed the comprehensive literature search following the predetermined inclusion and exclusion criteria. A methodological quality assessment was carried out using a scoring protocol and the risk of bias in the studies was analyzed. Reward screening was performed among the selected articles to perform a meta-analysis based on the pre-determined criteria. Case groups where α-mangostin extracted from Garcinia mangostana was incorporated were compared to groups using different antibiotics or antiseptic agents (control) to evaluate their effectiveness. A total of 30 studies were included; they were heterogeneous in their study design and the risk of bias was moderate. The results showed a reduction in microbial counts after the incorporation of α-mangostin, which resulted in better disinfection and effectiveness against multiple microbes. Additionally, the meta-analysis result revealed no significant difference (p > 0.05) in their effectiveness when α-mangostin was compared to commercially available antibiotics. α-mangostin worked effectively against the tested microbes and was shown to have inhibitory effects on microbes with antibiotic resistance.
RESUMO
Apical membrane antigen 1 (AMA1) of the malaria parasite Plasmodium falciparum has been implicated in the invasion of host erythrocytes and is an important vaccine candidate. We have previously described a 20-residue peptide, R1, that binds to AMA1 and subsequently blocks parasite invasion. Because this peptide appears to target a site critical for AMA1 function, it represents an important lead compound for anti-malarial drug development. However, the effectiveness of this peptide inhibitor was limited to a subset of parasite isolates, indicating a requirement for broader strain specificity. Furthermore, a barrier to the utility of any peptide as a potential therapeutic is its susceptibility to rapid proteolytic degradation. In this study, we sought to improve the proteolytic stability and AMA1 binding properties of the R1 peptide by systematic methylation of backbone amides (N-methylation). The inclusion of a single N-methyl group in the R1 peptide backbone dramatically increased AMA1 affinity, bioactivity, and proteolytic stability without introducing global structural alterations. In addition, N-methylation of multiple R1 residues further improved these properties. Therefore, we have shown that modifications to a biologically active peptide can dramatically enhance activity. This approach could be applied to many lead peptides or peptide therapeutics to simultaneously optimize a number of parameters.
