Quinones from Cordia species from 1972 to 2023: isolation, structural diversity and pharmacological activities.

Plants of the genus Cordia (Boraginaceae family) are widely distributed in the tropical regions of America, Africa, and Asia. They are extensively used in folk medicine due to their rich medicinal properties. This review presents a comprehensive analysis of the isolation, structure, biogenesis, and biological properties of quinones from Cordia species reported from 1972 to 2023. Meroterpenoids were identified as the major quinones in most Cordia species and are reported as a chemotaxonomic markers of the Cordia. In addition to this property, quinones are reported to display a wider and broader spectrum of activities, are efficient scaffold in biological activity, compared to other classes of compounds reported in Cordia, hence our focus on the study of quinones reported from Cordia species. About 70 types of quinones have been isolated, while others have been identified by phytochemical screening or gas chromatography. Although the biosynthesis of quinones from Cordia species is not yet fully understood, previous reports suggest that they may be derived from geranyl pyrophosphate and an aromatic precursor unit, followed by oxidative cyclization of the allylic methyl group. Studies have demonstrated that quinones from this genus exhibit antifungal, larvicidal, antileishmanial, anti-inflammatory, antibiofilm, antimycobacterial, antioxidant, antimalarial, neuroinhibitory, and hemolytic activities. In addition, they have been shown to exhibit remarkable cytotoxic effects against several cancer cell lines which is likely related to their ability to inhibit electron transport as well as oxidative phosphorylation, and generate reactive oxygen species (ROS). Their biological activities indicate potential utility in the development of new drugs, especially as active components in drug-carrier systems, against a broad spectrum of pathogens and ailments.

Antiplasmodial and Antileishmanial Activities of a New Limonoid and Other Constituents from the Stem Bark of Khaya senegalensis.

Plasmodium falciparum and Leishmania sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant socioeconomic impacts, and mostly affect disadvantaged populations living in remote tropical areas. This challenge emphasizes the need to search for new chemical scaffolds that preferably possess novel modes of action to contribute to antimalarial and antileishmanial research programs. This study aimed to investigate the antimalarial and antileishmanial properties of a methanol extract (KS-MeOH) of the stem bark of the Cameroonian medicinal plant Khaya senegalensis and its isolated compounds. The purification of KS-MeOH led to the isolation of a new ordered limonoid derivative, 21ß-hydroxybourjotinolone A (1a), together with 15 known compounds (1bc-14) using a repeated column chromatography. Compound 1a was obtained in an epimeric mixture of 21α-melianodiol (1b) and 21ß-melianodiol (1c). Structural characterization of the isolated compounds was achieved with HRMS, and 1D- and 2D-NMR analyses. The extracts and compounds were screened using pre-established in vitro methods against synchronized ring stage cultures of the multidrug-resistant Dd2 and chloroquine-sensitive/sulfadoxine-resistant 3D7 strains of Plasmodium falciparum and the promastigote form of Leishmania donovani (1S(MHOM/SD/62/1S). In addition, the samples were tested for cytotoxicity against RAW 264.7 macrophages. Positive controls consisted of artemisinin and chloroquine for P. falciparum, amphotericin B for L. donovani, and podophyllotoxin for cytotoxicity against RAW 264.7 cells. The extract and fractions exhibited moderate to potent antileishmanial activity with 50% inhibitory concentrations (IC50) ranging from 5.99 ± 0.77 to 2.68 ± 0.42 µg/mL, while compounds displayed IC50 values ranging from 81.73 ± 0.12 to 6.43 ± 0.06 µg/mL. They were weakly active against the chloroquine-sensitive/sulfadoxine-resistant Pf3D7 strain but highly potent toward the multidrug-resistant PfDd2 (extracts, IC50 2.50 ± 0.12 to 4.78 ± 0.36 µg/mL; compounds IC50 2.93 ± 0.02 to 50.97 ± 0.37 µg/mL) with selectivity indices greater than 10 (SIDd2 > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21ß-hydroxylbourjotinolone A (1a) + 21α-melianodiol (1b) + 21ß-melianodiol (1c)] exhibited moderate activity against P. falciparum and L. donovani. This novel antiplasmodial and antileishmanial chemical scaffold qualifies as a promising starting point for further medicinal chemistry-driven development of a dually active agent against two major infectious diseases affecting humans in Africa.

HPLC-Based Purification and Isolation of Potent Anti-HIV and Latency Reversing Daphnane Diterpenes from the Medicinal Plant Gnidia sericocephala (Thymelaeaceae).

Despite the success of combination antiretroviral therapy (cART), HIV persists in low- and middle-income countries (LMIC) due to emerging drug resistance and insufficient drug accessibility. Furthermore, cART does not target latently-infected CD4+ T cells, which represent a major barrier to HIV eradication. The "shock and kill" therapeutic approach aims to reactivate provirus expression in latently-infected cells in the presence of cART and target virus-expressing cells for elimination. An attractive therapeutic prototype in LMICs would therefore be capable of simultaneously inhibiting viral replication and inducing latency reversal. Here we report that Gnidia sericocephala, which is used by traditional health practitioners in South Africa for HIV/AIDS management to supplement cART, contains at least four daphnane-type compounds (yuanhuacine A (1), yuanhuacine as part of a mixture (2), yuanhuajine (3), and gniditrin (4)) that inhibit viral replication and/or reverse HIV latency. For example, 1 and 2 inhibit HIV replication in peripheral blood mononuclear cells (PBMC) by >80% at 0.08 µg/mL, while 1 further inhibits a subtype C virus in PBMC with a half-maximal effective concentration (EC50) of 0.03 µM without cytotoxicity. Both 1 and 2 also reverse HIV latency in vitro consistent with protein kinase C activation but at 16.7-fold lower concentrations than the control prostratin. Both 1 and 2 also reverse latency in primary CD4+ T cells from cART-suppressed donors with HIV similar to prostratin but at 6.7-fold lower concentrations. These results highlight G. sericocephala and components 1 and 2 as anti-HIV agents for improving cART efficacy and supporting HIV cure efforts in resource-limited regions.

Evaluation of Trace Metal Profile in Cymbopogon validus and Hyparrhenia hirta Used as Traditional Herbs from Environmentally Diverse Region of Komga, South Africa.

FAAS was used for the analysis of trace metals in fresh and dry plant parts of Cymbopogon validus and Hyparrhenia hirta species with the aim of determining the trace metals concentrations in selected traditional plants consumed in Eastern Cape, South Africa. The trace metal concentration (mg/kg) in the samples of dry Cymbopogon validus leaves (DCVL) showed Cu of 12.40 ± 1.000; Zn of 2.42 ± 0.401; Fe of 2.50 ± 0.410; Mn of 1.31 ± 0.210; Pb of 3.36 ± 0.401 mg/kg, while the samples of fresh Hyparrhenia hirta flowers (FHHF) gave Cu of 9.77 ± 0.610; Zn of 0.70 ± 0.200; Fe of 2.11 ± 0.200; Mn of 1.15 ± 0.080; Pb of 3.15 ± 0.100 mg/kg. Abundance of metal concentrations follows the order: Cu > Fe > Pb > Mn > Zn in the flower samples of Cymbopogon validus and Hyparrhenia hirta species. The concentrations of trace metals in both plant parts were below the permissible limits (PL) set by WHO. It is suggested that pharmacovigilance be carried out periodically to improve the quality, safety, and efficiency of various herbal products.