Cristina Moiteiro

Antioxidant Capacity of the Essential Oils From Lavandula luisieri, L. stoechas subsp. lusitanica, L. stoechas subsp. lusitanica x L. luisieri and L. viridis Grown in Algarve (Portugal)

Abstract The antioxidant capacity of the essential oils isolated from the aerial parts of Lavandula luisieri, L. stoechas subsp. lusitanica, the hybrid L. stoechas subsp. lusitanica x L. luisieri, and L. viridis collected in different regions of Algarve (Portugal), as well as that of butylated hydroxytoluene (BHT), was evaluated using three different methods: free radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, thiobarbituric acid reactive substances assay (TBARS) and reductive potential. The chemical composition of the essential oils was analyzed by GC and GC/MS. The oils of L. luisieri were mainly constituted by 1,8-cineole (26–34%) and trans-α-necrodyl acetate (11–18%), only present in this lavender species. The oils of Lavandula stoechas subsp. lusitanica and the hybrid L. stoechas subsp. lusitanica x L. luisieri were dominated by fenchone (42–44%) and camphor (35–36%). Despite of the morphological resemblances of the L. stoechas subsp. lusitanica x L. luisieri with L. luisieri, no necrodane derivatives were detected in the hybrid, showing instead a major chemical similarity with L. stoechas oil. Lavandula viridis oil mainly comprised 1,8-cineole (33%) and camphor (20%). The oils of L. luisieri were the most effective as antioxidants, independent of the evaluation method used, although showing always lower antioxidant ability than BHT.

Synthesis and evaluation of rifabutin analogs against Mycobacterium avium and H37Rv, MDR and NRP Mycobacterium tuberculosis

Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity. RBT analogs 2-11 were synthesized and evaluated against M. avium 1581 and Mycobacterium tuberculosis susceptible and resistant strains in vitro. A selection of candidates were also assayed against non-replicating persistent (NRP) M. tuberculosis. Subsequent in vivo studies with the best preclinical candidate drugs 5 and 8, in a model of progressive pulmonary tuberculosis of Balb/C mice infected either with H(37)Rv drug-sensible strain or with multidrug resistant (MDR) clinical isolates, resistant to all primary antibiotics including rifampicin, were performed. The results disclosed here suggest that 5 and 8 have potential for clinical application.

Antimycobacterial Metabolites from Plectranthus: Royleanone Derivatives against Mycobacterium tuberculosis Strains

The antimycobacterial activities of eight diterpenes, 1–8, isolated previously from Plectranthus and eleven esters, 9–19, of 7α‐acetoxy‐6β,12‐dihydroxyabieta‐8,12‐diene‐11,14‐dione (5) were evaluated against the MTB strains H37Rv and MDR. Only diterpenoids with a quinone framework revealed anti‐MTB activity. Abietane 5 and its 6,12‐dibenzoyl, 12‐methoxybenzoyl, 12‐chlorobenzoyl, and 12‐nitrobenzoyl esters, 9, 11, 12, and 13, respectively, showed potent activities against the MDR strain with MIC values between 3.12 and 0.39 μg/ml. Cytotoxic activities towards 3T3 and Vero cells were also evaluated. Compound 11, with the best selectivity index, may be a suitable lead for further chemical modifications. The complete structural elucidation of the new esters, 9–14, 16, 18, and 19, as well as the NMR data of known derivatives 15 and 17 are reported.

Differential Interactions of Rifabutin with Human and Bacterial Membranes: Implication for Its Therapeutic and Toxic Effects

This work focuses on the interaction of rifabutin (RFB), a naphthalenic ansamycin, with membrane models. Since the therapeutic and toxic effects of this class of drugs are strongly influenced by their lipid affinity, we concerned specifically on the ability of this antibiotic to affect the membrane biophysical properties. The extent of the interaction between RFB and membrane phospholipids was quantified by the partition coefficient (K(p)), using membrane model systems that mimic the human (liposomes of 1,2-dimyristoyl-sn-glycero-phosphocholine, DMPC) and the bacterial (liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol, DMPG) plasma membranes. To predict the drug location in the membranes, fluorescence quenching and lifetime measurements were carried out using the above-mentioned membrane models labeled with fluorescent probes. Steady-state anisotropy measurements were also performed to evaluate the effect of RFB on the microviscosity of the membranes. Overall, the results support that RFB has higher affinity for the bacterial membrane mediated by electrostatic interactions with the phospholipid head groups.

COMPOSITION AND BIOLOGICAL ACTIVITY OF THE ESSENTIAL OIL OF PERUVIAN LANTANA CAMARA

The composition of the essential oil from Lantana camara L. (Verbenaceae) obtained by hydrodistillation of the aerial parts was examined by GC, GC/ MS, and 13C-NMR. The GC analysis showed that carvone is the most abundant monoterpene 75.9%, together with limonene 16.9%, accounting for 92.8% of the oil. The major components were also tested by 13C-NMR analysis of the essential oil. The L. camara oil was assayed against several microorganisms, showing moderate antibacterial activity against the human pathogen Staphylococcus aureus (MIC 200 µg/ml). High antioxidant activity evaluated by the Trolox equivalent antioxidant capacity assay (TEAC) was found (29.0 mmol Trolox/kg) and relative low anti-inflammatory activity due to its weak ability for inhibiting lipoxygenase (IC 50 = 81.5 µg/ml).

COMPOSITION AND ANTIMICROBIAL SCREENING OF THE ESSENTIAL OIL FROM THE LEAVES AND STEMS OF Senecio atacamensis Phil. FROM CHILE

An essential oil from Senecio atacamensis Phil. (Asteraceae) was obtained by hydrodistillation of its aerial parts (leaves and stems) and its composition was determined by GC and GC/MS analysis. The identification by GC of the essential oil components, in both leaves and stems respectively, showed α-terpinene (36.05% and 20.57%); α-phellandrene (27.79% and 25.37%), and p-cymene (11.85% and 22.55%) as the most abundant monoterpenes. Furthermore, the oil was tested for its antimicrobial activity using paper disc diffusion and the dilution broth method, exhibiting moderate inhibition of human pathogenic bacteria.

The influence of rifabutin on human and bacterial membrane models: implications for its mechanism of action.

This work focuses on the interaction of the antibiotic Rifabutin (RFB) with phospholipid membrane models using small- and wide-angle X-ray scattering (SAXS and WAXS) to assess drug-membrane interactions. The effect of different concentrations of RFB on human and bacterial cell membrane models was studied using multilamellar vesicles (MLVs) at the physiological pH (7.4). In this context, MLVs of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) were chosen to mimic the human cell membrane. To mimic the bacterial cell membrane, 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) (8:2 molar ratio) were used. The results support a perturbation of the lipid bilayers caused by RFB, especially in the bacterial membrane model, inducing phase separation that might compromise the integrity of the bacterial membrane. Therefore, the different effects of this antibiotic depending on the concentration, the charge of the phospholipid headgroup, and the membrane organization may be related with the RFB antibiotic activity and the side effects, and should be accounted for during the anti-tuberculosis (anti-TB) drug design.

Antiparasitic Activity of Diterpenoids Against Trypanosoma cruzi.

Twenty-seven diterpenes, including abietanes, labdanes, abeoabietanes, halimanes, and pimaranes, have been evaluated against epimastigote and intracellular amastigote forms of Trypanosoma cruzi and also against LC5 and NCTC cell lines. Royleanones (3, 4, and 5) and a further abietane (12), obtained by purification of Plectranthus spp. extracts, were the most active compounds on epimastigotes, showing IC50 values similar (1.73 µg/mL, 12) or even lower (0.39, 0.99, and 1.20 µg/mL, 3, 4, and 5 respectively) than the positive control nifurtimox (2.3 µg/mL). On intracellular amastigotes, abietanes 3, 4, and 5 showed a significant activity with IC50 values of 0.83, < 0.31, and 0.62 µg/mL, respectively, but were less potent than the positive control nifurtimox (IC50 < 0.16 µg/mL). Compounds 3, 4, and 5 were not cytotoxic to LC5 and NCTC 929 cells at 1 µg/mL.