Liliana Betancur-Galvis

Cytotoxic and Antiviral Activities of Colombian Medicinal Plant Extracts of the Euphorbia genus

Forty-seven plant extracts of 10 species of the genus Euphorbia (Euphorbiaceae) used by Colombian traditional healers for the treatment of ulcers, cancers, tumors, warts, and other diseases, were tested in vitro for their potential antitumour (antiproliferative and cytotoxic) and antiherpetic activity. To evaluate the capacity of the extracts to inhibit the lytic activity of herpes simplex virus type 2 (HSV-2) and the reduction of viability of infected or uninfected cell cultures, the end-point titration technique (EPTT) and the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] colorimetric assay were used, respectively. The therapeutic index of the positive extracts for the antiviral activity was determined by calculating the ratio CC50 (50% cytotoxic concentration) over IC50 (50% inhibitory concentration of the viral effect). Five of the 47 extracts (11%) representing 3 out of 10 Euphorbia species (30%) exhibited antiherpetic action; the highest activity was found in the leaf/stem water-methanol extracts from E. cotinifolia and E. tirucalli. The therapeutic indexes of these two plant species were > 7.1; these extracts exhibited no cytotoxicity. Six extracts (13%) representing 4 plant species (40%) showed cytotoxic activity. The highest cytotoxicity was found in the dichloromethane extract obtained from E. cotinifolia leaves and the CC50 values for the most susceptible cell lines, HEp-2 and CHO, were 35.1 and 18.1 microgram/ml, respectively.

Antitumor and Antiviral Activity of Colombian Medicinal Plant Extracts

Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity) and antiherpetic activity. MTT (Tetrazolium blue) and Neutral Red colorimetric assays were used to evaluate the reduction of viability of cell cultures in presence and absence of the extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type 2 (HSV-2). The 50% cytotoxic concentration (CC50) and the 50% inhibitory concentration of the viral effect (EC50) for each extract were calculated by linear regression analysis. Extracts from Annona muricata, A. cherimolia and Rollinia membranacea, known for their cytotoxicity were used as positive controls. Likewise, acyclovir and heparin were used as positive controls of antiherpetic activity. Methanolic extract from Annona sp. on HEp-2 cells presented a CC50 value at 72 hr of 49.6x10(3)mg/ml. Neither of the other extracts examined showed a significant cytotoxicity. The aqueous extract from Beta vulgaris, the ethanol extract from Callisia grasilis and the methanol extract Annona sp. showed some antiherpetic activity with acceptable therapeutic indexes (the ratio of CC50 to EC50). These species are good candidates for further activity-monitored fractionation to identify active principles.

Citral and carvone chemotypes from the essential oils of Colombian Lippia alba (Mill.) N.E. Brown: composition, cytotoxicity and antifungal activity.

Two essential oils of Lippia alba (Mill.) N.E. Brown (Verbenacea), the carvone and citral chemotypes and 15 of their compounds were evaluated to determine cytotoxicity and antifungal activity. Cytotoxicity assays for both the citral and carvone chemotypes were carried out with tetrazolium-dye, which showed a dose-dependent cytotoxic effect against HeLa cells. Interestingly, this effect on the evaluated cells (HeLa and the non-tumoural cell line, Vero) was lower than that of commercial citral alone. Commercial citral showed the highest cytotoxic activity on HeLa cells. The antifungal activity was evaluated against Candida parapsilosis, Candida krusei, Aspergillus flavus and Aspergillus fumigatus strains following the standard protocols, Antifungal Susceptibility Testing Subcommittee of the European Committee on Antibiotic Susceptibility Testing and CLSI M38-A. Results demonstrated that the most active essential oil was the citral chemotype, with geometric means-minimal inhibitory concentration (GM-MIC) values of 78.7 and 270.8 microg/mL for A. fumigatus and C. krusei, respectively. Commercial citral showed an antifungal activity similar to that of the citral chemotype (GM-MIC values of 62.5 microg/mL for A. fumigatus and 39.7 microg/mL for C. krusei). Although the citronellal and geraniol were found in lower concentrations in the citral chemotype, they had significant antifungal activity, with GM-MIC values of 49.6 microg/mL for C. krusei and 176.8 microg/mL for A. fumigatus.

Synthesis and biological evaluation of dehydroabietic acid derivatives

A series of C18-oxygenated derivatives of dehydroabietic acid were synthesized from commercial abietic acid and evaluated for their cytotoxic, antimycotic, and antiviral activities.

Synthesis and biological evaluation of abietic acid derivatives.

A series of C18-oxygenated derivatives of abietic acid were synthesized and evaluated for their cytotoxic, antimycotic, and antiviral activities. In general, the introduction of an aldehyde group at C18 did improve the resultant bioactivity, while the presence of an acid or alcohol led to less active compounds.

Synthesis and cytotoxic activity of novel C7-functionalized spongiane diterpenes.

Based on two lead cytotoxic spongiane diterpenes, a new series of C7-oxygenated derivatives were synthesized and evaluated for their antitumor activity in vitro against the cancer cell lines HeLa and HEp-2. In general, introduction of either hydroxyl or acetoxy groups at C-7 did not improve the resultant cytotoxicity, while the presence of a butyrate ester led to more active compounds (CC(50)=4.0-9.5 microM).

Synthesis and biological evaluation of (+)-labdadienedial, derivatives and precursors from (+)-sclareolide

Labdadienedial and a series of C15,C16-functionalized derivatives were synthesized from commercial (+)-sclareolide and evaluated for their cytotoxic, antimycotic, and antiviral activities. Their precursors were similarly evaluated.

Cytotoxic, immunomodulatory, antimycotic, and antiviral activities of semisynthetic 14-hydroxyabietane derivatives and triptoquinone C-4 epimers

A series of C14-hydroxy derivatives of dehydroabietic acid were synthesised from commercial abietic acid and evaluated for their cytotoxic, antimycotic, and antiviral activities. From these C14-hydroxy derivatives, triptoquinone C-4 epimers were obtained and their immunomodulatory activity was additionally evaluated. None of the tested compounds showed antiviral activity against herpes simplex virus type 1 (HHV-1), and nor did they display antimycotic activity against certain Aspergillus, spp. except for one compound, abieta-8,11,13-trien-14,18-diol. Interestingly, two triptoquinone epimers showed cytotoxic activity, and one of them induced mitochondrial potential loss, DNA damage and cell cycle distribution alterations in Jurkat cells, but not in human peripheral blood mononuclear cells. In addition, these compounds inhibited monocytes differentiation and production of pro-inflammatory cytokines, IL-1β and TNF-α, and the anti-inflammatory cytokine IL-10 in the presence of LPS. In conclusion, one of the triptoquinone molecules could be a promising scaffold for the development of novel anti-cancer agents, and two of them could be potential anti-inflammatory agents.

Cytotoxic activity of Asteraceae and Verbenaceae family essential oils

Thirty-six essential oils from Verbenaceae and Asteraceae family plants along with their major constituents were evaluated to determine cytotoxicity on Jurkat, HeLa, HepG2 and Vero cell lines. The plants were collected in different regions of Colombia, and their essential oils were extracted through microwave-assisted hydrodistillation and then characterized through GC/MS and GC/FID analyses. Cytotoxic activity testing was carried out using a tetrazolium-dye (MTT) assay. The essential oils from Lippia alba Citral and Carvone chemotypes showed the lowest IC50 and selectivity index (IS) > 10. The essential oils from Asteraceae family were not selective against the tumor cell lines tested. Citral chemotype L. alba essential oils showed values up to 27.2, and Carvone chemotype L. alba essential oils showed values up to 30.7. Citral, showed the highest cytotoxic activity, with an SI value of 1241, and Limonene and Linalool showed SI values of 6.97 and 10.1, respectively, on HeLa cells.

Antifungal activity and chemical composition of the essential oils of Lippia alba (Miller) N.E Brown grown in different regions of Colombia.

Abstract The essential oils from Lippia alba (Miller) N.E Brown (Verbenaceae Family) collected in different regions of Colombia were obtained by microwave-assisted hydrodistillation. Their chemical compositions were determined by GC and GC/MS. Two chemotypes were distinguished, characterized by carvone and citral as main constituents. Antifungal activity of the essential oils was determined following the standard microdilution protocols AFST-EUCAST for C. krusei and C. parasilopsis, and CLSI-M38A for Aspergillus fumigatus and A. flavus. The essential oils obtained from both L. alba chemotypes showed antifungal activity.