Isaac Tuffour

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus

Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-κB and MAPK signaling pathways because either overexpression of a super-repressor form of IκBα or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-κB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs.

Spectroscopic Characterization, In Vitro Cytotoxicity, and Antioxidant Activity of Mixed Ligand Palladium(II) Chloride Complexes Bearing Nucleobases

Mixed-ligand palladium(II) chloride complexes bearing the nucleobases, adenine (Ad), cytosine (Cyt), and guanine (Gua), have been synthesized and characterized by UV-vis spectrophotometric methods, magnetic susceptibility, molar conductivity, elemental analysis, FTIR, and 1H-NMR. The complexes were found to have the composition cis-[PdCl2(Gua)(Cyt)], cis-[PdCl2(Ad)(Cyt)], and cis-[PdCl2(Ad)(Gua)]. A four-coordinated square-planar geometry is proposed for these Pd(II) complexes based on magnetic evidence and electronic spectra. The complexes as well as the free nucleobase ligands were tested for their in vitro cytotoxicity on human promyelocytic leukemia (HL60) and human histiocytic leukemia (U937) cell lines. cis-[PdCl2(Ad)(Gua)] showed IC50 values of 11.29 ± 2.91 and 8.31 ± 1.44 μM against HL60 and U937, respectively, which was higher than that of the positive control (curcumin) against U937. The complexes also showed significant antioxidant activity when tested against 2,2-diphenyl-1-picrylhydrazylradical (DPPH).

Extracts of Codiaeum variegatum (L.) A. Juss is Cytotoxic on Human Leukemic, Breast and Prostate Cancer Cell Lines -

The high cost of treatment of cancer coupled with the emergence of drug resistance makes it imperative for new drug interventions to curb its occurrence. Hence, the objective of this research was to determine the phytochemical, total phenolic content, antioxidant and antiproliferative effect of Codiaeum variegatum crude extracts and fractions. The MTT cell viability and DPPH assays among others were used to determine the selected properties of the plants. The presence of general glycosides, tannins, alkaloids, flavonoids and sterols was observed in its stem bark and leaf. Triterpenoids were present in the leaf only while saponins were observed in the stem bark only. Strong antioxidant activities were observed in both stem bark and leaf with EC50 values of 0.053±0.004 mg/mL and 1.396±0.073 mg/mL respectively. Both crude extracts showed antiproliferative activity towards all cancer cell lines with the stem bark exhibiting the strongest cytotoxicity. However, both showed strong cytotoxicity towards normal cells as well. The mechanism of cell death was determined to be apoptosis. Further testing of fractions from its stem bark crude extract revealed an increase in cytotoxicity of its chloroform fraction against Jurkat cells with an IC50 of 44.71±0.44 µg/mL. These results confirm the cytotoxicity of this plant.

Constituents of the Roots of Dichapetalum pallidum and Their Anti-Proliferative Activity

As part of our search for bioactive compounds from the Dichapetalaceae, repeated chromatographic purification of the roots of a hitherto unexamined species, Dichapetalum pallidum, led to the isolation of the newly occurring 7-hydroxydichapetalin P (1) and the known dichapetalins A (2) and X (3). Also isolated were the known compounds friedelin-2,3-lactone (4), friedelan-3-one (6), friedelan-3β-ol (7) and pomolic (8), as well as the dipeptide aurantiamide acetate (5). The compounds were characterized by direct interpretation of their IR, 1D NMR and 2D NMR spectral data and by comparison of their physico-chemical data, including their chromatographic profiles, with the literature and authentic samples in our compound library for the genus Dichapetalum. The compounds were assayed for their anti-proliferative activities against the human T-lymphocytic leukemia (Jurkat), acute promyelocytic leukemia (HL-60) and T-lymphoblast-like leukemia (CEM) cell lines. Overall, dichapetalin X showed the strongest (3.14 μM) and broadest cytotoxic activities against all the leukemic cell lines tested, exhibiting even stronger activities than the standard compound, curcumin.