William Gustavo Lima

Phytochemical characterisation and bioprospection for antibacterial and antioxidant activities of Lippia alba Brown ex Britton & Wilson (Verbenaceae)

Abstract Ethanol extract and fractions obtained from fresh and dry aerial parts of Lippia alba were examined in order to determine their phytochemical composition, antioxidant capacity and antibacterial activities. The ethanol extracts and fractions exhibited an antioxidant effect by the DPPH assay, especially samples of fresh plant. HPLC analysis of the ethyl acetate fractions identified the presence of phenolic acids and flavonoids. The ethanol extract and fractions showed activity against reference and multidrug-resistant strains of Staphylococcus aureus and Enterococcus faecalis (MIC range 2000–250 μg/mL). The hexane and dichloromethane fractions of fresh plant showed better activity against reference strains of Escherichia coli (MIC of 250 and 125 μg/mL, respectively), but all extracts and fractions were less active against multidrug-resistant strains of all the Gram-negative species evaluated. The results showed that the extract and fractions of L alba aerial parts showed antibacterial activity, even against multidrug-resistant Gram-positive bacteria, and antioxidant effect (DPPH assay).

Chromosomally encoded and plasmid-mediated polymyxins resistance in Acinetobacter baumannii: a huge public health threat

Acinetobacter baumannii is an opportunistic pathogen associated with nosocomial and community infections of great clinical relevance. Its ability to rapidly develop resistance to antimicrobials, especially carbapenems, has re-boosted the prescription and use of polymyxins. However, the emergence of strains resistant to these antimicrobials is becoming a critical issue in several regions of the world because very few of currently available antibiotics are effective in these cases. This review summarizes the most up-to-date knowledge about chromosomally encoded and plasmid-mediated polymyxins resistance in A. baumannii. Different mechanisms are employed by A. baumannii to overcome the antibacterial effects of polymyxins. Modification of the outer membrane through phosphoethanolamine addition, loss of lipopolysaccharide, symmetric rupture, metabolic changes affecting osmoprotective amino acids, and overexpression of efflux pumps are involved in this process. Several genetic elements modulate these mechanisms, but only three of them have been described so far in A. baumannii clinical isolates such as mutations in pmrCAB, lpxACD, and lpsB. Elucidation of genotypic profiles and resistance mechanisms are necessary for control and fight against resistance to polymyxins in A. baumannii, thereby protecting this class for future treatment.

Docking and QM/MM Studies of NS2B-NS3pro Inhibitors: a Molecular Target against the Dengue Virus

Dengue virus (DENV) has been characterized as having great clinical importance in the world, as there is no specific treatment against this virus. The NS2B-NS3pro complex is essential for the replication and maturation of DENV and is a potential pharmacological target. The present study aims to evaluate and understand the interactions and affinities (via molecular docking/AutoDock Vina) of 16 peptidomimetic derivatives applied to a NS2B-NS3pro DENV-2 complex constructed by homology modeling (via SWISS-MODEL). Two compounds were selected as potential inhibitors of this protein complex. In addition, these compounds possess important interactions involving Ser135, Gly169 and Tyr161, which have been described previously to be fundamental to the recognition of inhibitors directed to this receptor. Thus, the involvement of these residues is significant pharmacologically because they may contribute to the inhibitory action of this molecular target against DENV.

Antibiotic resistance profile and occurrence of AmpC between Pseudomonas aeruginosa isolated from a domestic full-scale WWTP in southeast Brazil

Wastewater treatment plants (WWTPs) represent an important reservoir of antibiotic resistance determinants. Although many studies have been conducted to evaluate resistance profiles in Enterobacteriaceae isolates from this setting, the dynamics of this phenomenon are poorly known to the bacterium Pseudomonas aeruginosa. Here we aimed to evaluate the resistance profiles and the production of AmpC β-lactamase in P. aeruginosa isolates from a domestic full-scale WWTP. Samples of the raw sewage and effluent were collected and the bacterium P. aeruginosa was isolated on cetrimide agar. Susceptibility to β-lactams, fluoroquinolones and aminoglycosides was evaluated by the disc diffusion method, and the presence of AmpC β-lactamase was investigated phenotypically and by molecular method. We recovered 27 isolates of P. aeruginosa. Of these, 81.5% were susceptible to all antimicrobials tested. However, a considerable rate of resistance to carbapenems (11%) was found among the isolates. Twenty-two isolates were positive in the phenotypic test for inducible AmpC β-lactamase but the blaampc gene was only identified in four isolates, suggesting the presence of other independent resistance mechanisms besides this β-lactamase. In summary, we have shown that P. aeruginosa isolates from a domestic WWTP represents a potential reservoir of blaampC genes and other resistance determinants, including those that result in low susceptibility to carbapenems and aminoglycosides.

Design, synthesis, biological activity and structure-activity relationship studies of chalcone derivatives as potential anti- Candida agents

Vulvovaginal candidiasis (VVC) affects millions of women around the world every year. Candida albicans is the most frequently isolated pathogen in women and its rapid ability to develop resistance to first and second line therapies has boosted the search for new and effective antifungal agents. In this study, we show the in vitro anti-Candida activity of fifteen synthetic chalcone analogs and their antifungal potential in an in vivo model of VVC. Chalcone 12 showed potent antifungal effects, being able to inhibit the growth of Candida spp. at a concentration of 15.6 µg mL−1. In addition, mechanism of action studies have indicated the ergosterol fungal membrane as the target of this compound. Despite a considerable antifungal activity, the chalcone 12 showed high cytotoxicity in kidney cells lineages. Moreover, this compound was able to reduce Candida-associated virulence, impairing yeast–hyphal transition in C. albicans. An in vivo model of VVC showed that chalcone 12 significantly reduces the fungal load. Taken together, these findings showed that the chalcone 12 is a potent anti-Candida agent in vitro beyond of contribute to improve the fungal infection in a model of CVV. However, it showed low selectivity and high toxicity, suggesting molecular modifications to minimize these proprieties.

Chemical characterization and bioherbicidal potential of the essential oil from the leaves of Unonopsis guatterioides (A.DC.) R.E.Fr. (Annonaceae)

Abstract The chemical composition and the phytotoxicity potential of the essential oil from leaves of Unonopsis guatterioides (A.DC.) R.E.Fr. (Annonaceae) was investigated. Gas chromatography/mass spectrometry analyses revealed 16 constituents representing 99.50% of the total essential oil, composed mainly of sesquiterpenes. α-copaene, bicyclogermacrene and trans-caryophyllene were the major components (15.7% each), followed by α-humullene, allo-aromadendrene and (+)-spathulenol (9.0, 8.4 and 7.3%, respectively). The essential oil inhibited seed germination and growth in both monocotyledon (Allium cepa) and dicotyledon (Lactuca sativa) models, pointing to a promising application of this oil obtained from the leaves of U. guatterioides as a new bioherbicide.