Browsing by Author "Lerata, Mookho S."

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    Encapsulation of variabilin in stearic acid solid lipid nanoparticles enhances its anticancer activity in vitro
    (MDPI, 2020) Lerata, Mookho S.; D’Souza, Sarah; Sibuyi, Nicole Remaliah Samantha
    The use of natural products as chemotherapeutic agents is well established; however, many of these are associated with undesirable side effects, including high toxicity and instability. Furthermore, the development of drug resistant cancers makes the search for new anticancer lead compounds a priority. In this study, the extraction of an Ircinia sp. sponge resulted in the isolation of an inseparable mixture of (7E,12E,20Z)-variabilin (1) and (7E,12Z,20Z)-variabilin (2) and structural assignment was established using standard 1D and 2D NMR experiments. The cytotoxic activity of the compound against three solid tumour cell lines displayed moderate anti-cancer activity through apoptosis, together with a general lack of selectivity among the cancer cell lines studied. Structural assignment and cytotoxic evaluation of variabilin was complicated and further aggravated by its inherent instability. Variabilin was therefore incorporated into solid lipid nanoparticles (SLNs) and the stability and cytotoxic activity evaluated. Encapsulation of variabilin into SLNs led to a marked improvement in stability of the natural product coupled with enhanced cytotoxic activity, particularly against the prostate (PC-3) cancer cell line, with IC50 values of 87.74 µM vs. 8.94 µM for the variabilin alone and Var-SLN, respectively. Both variabilin and Var-SLN revealed comparable activity to Ceramide against the MCF-7 breast cancer cell line, revealing IC50 values of 34.8, 38.1 and 33.6 µM for variabilin, Var-SLN and Ceramide, respectively.
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    Green synthesized saunps as a potential delivery platform for cytotoxic alkaloids
    (MDPI, 2023) Mubaiwa, Byron; Lerata, Mookho S.; Sibuyi, Nicole R. S.
    The use of natural products as chemotherapeutic agents is well established. However, many are associated with undesirable side effects, including high toxicity and instability. Previous reports on the cytotoxic activity of pyrroloiminoquinones isolated from Latrunculid sponges against cancer cell lines revealed extraordinary activity at IC50 of 77nM for discorhabdins. Their general lack of selectivity against the cancer and normal cell lines, however, precludes further development. In this study, extraction of a South African Latrunculid sponge produced three known pyrroloiminoquinone metabolites (14-bromodiscorhabdin C (5), Tsitsikammamine A (6) and B (7)). The assignment of the structures was established using standard 1D and 2D NMR experiments. To mitigate the lack of selectivity, the compounds were loaded onto gold nanoparticles synthesized using the aqueous extract of a brown seaweed, Sargassum incisifolium (sAuNPs). The cytotoxicity of the metabolites alone, and their sAuNP conjugates, were evaluated together with the known anticancer agent doxorubicin and its AuNP conjugate. The compound-AuNP conjugates retained their strong cytotoxic activity against the MCF-7 cell line, with >90% of the pyrroloiminoquinone-loaded AuNPs penetrating the cell membrane.
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    Sutherlandiosides e−k: further cycloartane glycosides from sutherlandia frutescens
    (Elsevier Ltd, 2024) Tchegnitegni, Billy Toussie; Lerata, Mookho S.; Beukes, Denzil R.; Antunes, Edith M.
    A further chemical investigation of the butanol extract of leaves from the South African medicinal plant Sutherlandia frutescens led to the isolation of eight previously unreported saponins (1−8), together with the known sutherlandio sides A−D. Their structures were established by spectroscopic (1D and 2D NMR) analyses, CD, optical rotation, mass spectrometry, as well as chemical conversions. The isolates were screened for their cytotoxic activity against the MCF-7 human breast cancer cell line, although no significant activity was observed. In addition to the chemophenetic markers for this genus, i.e. the cycloartane glycosides, the present work also reports on the first isolation of an oleanan-type saponin from the Sutherlandia genus, forming an important fingerprint for the chemical composition of the plant.