Prenylated isoflavonoids from Millettia pervilleana

From the root bark of Millettia pervilleana, which had shown significant cytotoxic activity, a 3-phenylcoumarin, named pervilleanine, two new pterocarpans, pervilline and pervillinine, and one known, emoroidocarpan, were isolated in addition to rotenone and 3alpha-hydroxyrotenone. The anticancer activity of two previously isolated isoflavanones, pervilleanone and 3'-O-demethylpervilleanone is reported.     

Clerodane and labdane diterpenoids from Nuxia sphaerocephala

Seven diterpenoids including four clerodane and three labdane derivatives, (13S)-ent-7beta-hydroxy-3-cleroden-15-oic acid (1), ent-7beta-hydroxy-2-oxo-3-cleroden-15-oic acid (2), ent-2,7-dioxo-3-clero-den-15-oic acid (3), ent-18-(E)-caffeoyloxy-7beta-hydroxy-3-cleroden-15-oic acid (4) (13S)-ent-18-(E)-coumaroyloxy-8(17)-labden-15-oic acid (5), ent-18-(E)-caffeoyloxy-8(17)-labden-15-oic acid (6), ent-15-(E)-caffeoyloxy-8(17)-labden-18-oic acid (7), have been isolated from an ethyl acetate extract of the leaves of Nuxia sphaerocephala, together with 17 known compounds. 3-Oxolup-20(29)-en-30-al (3-oxolupenal) (8) and 3beta-hydroxylup-20(29)-en-30-al (3beta-hydroxy-lupenal) (9) showed the best inhibitory activity against Plasmodium falciparum with the IC(50) values between 1.55 and 4.67 microg/ml in vitro, respectively. The structure and the relative stereochemistry of the compounds were established on the basis of their spectroscopic properties. The absolute configuration at C-13 of 1 and 5 was determined by the PGME amide procedure.     

The impact of COVID-19 on clinical research for Neglected Tropical Diseases (NTDs): A case study of bubonic plague

BackgroundAmong the many collaterals of the COVID-19 pandemic is the disruption of health services and vital clinical research. COVID-19 has magnified the challenges faced in research and threatens to slow research for urgently needed therapeutics for Neglected Tropical Diseases (NTDs) and diseases affecting the most vulnerable populations. Here we explore the impact of the pandemic on a clinical trial for plague therapeutics and strategies that have been considered to ensure research efforts continue.MethodsTo understand the impact of the COVID-19 pandemic on the trial accrual rate, we documented changes in patterns of all-cause consultations that took place before and during the pandemic at health centres in two districts of the Amoron’I Mania region of Madagascar where the trial is underway. We also considered trends in plague reporting and other external factors that may have contributed to slow recruitment.ResultsDuring the pandemic, we found a 27% decrease in consultations at the referral hospital, compared to an 11% increase at peripheral health centres, as well as an overall drop during the months of lockdown. We also found a nation-wide trend towards reduced number of reported plague cases.DiscussionCOVID-19 outbreaks are unlikely to dissipate in the near future. Declining NTD case numbers recorded during the pandemic period should not be viewed in isolation or taken as a marker of things to come. It is vitally important that researchers are prepared for a rebound in cases and, most importantly, that research continues to avoid NTDs becoming even more neglected.     

Exploiting a basic chemosensitizing pharmacophore hypothesis. Part 1: synthesis and biological evaluation of novel arylbromide and bicyclic chemosensitizers against drug-resistant malaria parasites

An exploratory series of novel arylbromide and bicyclic chemosensitizers (modulators) against chloroquine-resistant Plasmodium falciparum were designed and synthesized on the basis of a basic chemosensitizing pharmacophore hypothesis in malaria. ortho-Substituted bromo and biphenyl ether compounds displayed the best activity from the series.     

The co-occurrence of C(3) epimer Nb,C(21)-secocuran alkaloids in Strychnos diplotricha and Strychnos myrtoides

From the stem bark of Strychnos diplotricha, three Nb,C(21)-secocuran alkaloids, viz., 3-epi-myrtoidine, 11-demethoxy-3-epi-myrtoidine and 11-demethoxy-12-hydroxy-3-epi-myrtoidine, were isolated together with the known myrtoidine and 11-demethoxymyrtoidine. They also occur in different parts of S. myrtoides.     

Chemical Composition and Biological Activities of the Essential Oil of Athanasia brownii Hochr. (Asteraceae) Endemic to Madagascar

The essential oil obtained from hydrodistillation of flowering aerial parts of Athanasia brownii (Asteraceae) was studied for its chemical composition by GC/FID and GC/MS, and for biological activity, namely, antioxidant, antimicrobial, and chemopreventive potential, by DPPH (=2,2‐diphenyl‐1‐picrylhydrazyl), ABTS (=2,2′‐azinobis[3‐ethylbenzothioline‐6‐sulfonic acid), and FRAP (=ferric reducing antioxidant power), disk diffusion test, and MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay, respectively. The oil was characterized by a high content of oxygenated sesquiterpenes (71.2%), with selin‐11‐en‐4α‐ol (24.6%), caryophyllene oxide (8.7%), humulene epoxide II (5.1%), and (E)‐nerolidol (4.9%) as the predominant compounds. The oil showed a moderate activity against streptococci as well as radical‐scavenging potential, while the inhibitory effects against human cancer cells examined such as A375 (malignant melanoma) and HCT 116 (colon carcinoma) were significant, with IC₅₀ values of 19.85 and 29.53 μg/ml, respectively.     

Ethnopharmacology and malaria: new hypothetical leads or old efficient antimalarials?

New treatments are urgently needed to curb and eradicate malaria in developing countries. As most people living in malarial endemic areas use traditional medicine to fight this disease, why have new treatments not emerged recently from ethnopharmacology-oriented research? The rationale and limitations of the ethnopharmacological approach are discussed in this paper, focusing on ethnopharmacology methodologies and techniques used for assessing botanical samples for their antimalarial properties. Discrepancies often observed between strong ethnopharmacological reputation and laboratory results are discussed, as well as new research perspectives.