Natural product based leads to fight against leishmaniasis.

Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs) affect more than 1 billion people annually, including 875 million children in developing economies. These diseases are also responsible for over 500,000 deaths per year and are characterized by long-term disability and severe pain. The impact of the combined NTDs closely rivals that of malaria and tuberculosis. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Natural products have been a valuable source of drug regimens that form the cornerstone of modern pharmaceutical care. In this review, we highlight the potential that remains untapped in natural products as drug leads for NTDs. We cover natural products from plant, marine, and microbial sources including natural-product-inspired semi-synthetic derivatives which have been evaluated against the various causative agents of NTDs. Our coverage is limited to four major NTDs which include human African trypanosomiasis (sleeping sickness), leishmaniasis, schistosomiasis and lymphatic filariasis.

https://www.mdpi.com/1420-3049/22/1/58/pdf

The Role of Natural Products in Drug Discovery and Development against Neglected Tropical Diseases

This review analyzes the more recent publications concerning the distribution, chemistry, and bioactivities of naphthoquinones (NQs) in higher plants. These highly reactive molecules have a diverse distribution in nature being isolated from bacteria, algae, fungi, lichens, insects, and higher plants, where they mostly occur in Eudicots. Over 200 species reported to produce NQs are listed according to orders and families. Out of 65 orders, only 16 report their occurrence, suggesting that the phylogenetically more advanced orders (Caryophyllales, Ericales, and Lamiales) have a higher percentage of NQ-producing families. Certain classes of NQs appear confined to certain orders. Chemically, the NQs found range from simple monomeric 1, 4- and 1, 2-NQ isomers to dimers, trimers, and tetramers, as well as furano, pyrano, and prenylated derivatives. The major bioactivities are summarized, including cytotoxicity and antitumor (a-dunnione, plumbagin, and shikonin), antibacterial (diospyrin), anti-inflammatory (iso-eleutherin), antiparasitic (sterekunthal A), antifungal (droserone). Some NQs are considered to be phytoalexins (e.g., O-hibiscanone induced by fungal infection of Hibiscus cannabinus with Verticillium dahliae ). Many of these activities are associated with their inhibition of electron transport, uncoupling of oxidative phosphorylation, and their intercalation with DNA. Many NQ-containing plants are of importance to humans, commercially as dyes (lawsone, shikonin) or as medicines in systems of Traditional Medicine (e.g., Lapacho, a herbal medicine used by South and Central American indigenous peoples to treat ailments including infection, fever, and stomach complaints). The review underlines the importance of NQs in taxonomy, chemistry, and their bioactive potential as novel biocides and chemotherapeutic agents.

Bioactive Naphthoquinones from Higher Plants

A total of 115 different plant extracts from our collection, representing 96 plant species, have been evaluated for in vitro antileishmanial activity against L. amazonensis promastigotes. In addition, the extracts were screened for cytotoxic activity against BALB/c mouse macrophages in order to assess a selectivity index. Crude extracts that showed a selectivity index (CC50 for macrophage / IC50 for promastigotes) ³ 5 or with IC50 < 12.5 μg/mL against promastigotes, a total of 28 extracts, were further screened for anti-amastigote activity. A total of 25 extracts showed promising activity against L. amazonensis promastigotes with low cytotoxic activity. Ten of these extracts showed selectivity indices, (CC50 for macrophages / IC50 for amastigotes) greater than 10 and are considered "hits", worthy candidates for further phytochemical exploration: Conostegia xalapensis methanol bark extract, Endiandra palmerstonii bark extract, Eugenia monteverdensis acetone bark extract, Eugenia sp. "fine leaf" acetone bark extract, Exothea paniculata chloroform bark extract, Mallotus paniculatus ethanol bark extract, Matelea pseudobarbata ethanol extract, Quercus insignis ethanol bark extract, Sassafras albidum dichloromethane bark extract, and Stemmadenia donnell-smithii acetone bark extract.

https://www.mdpi.com/2305-6320/1/1/32/pdf

Antileishmanial Potential of Tropical Rainforest Plant Extracts.

Extracts from the leaves of the Bangladeshi medicinal plant Terminalia citrina were prepared, and 13 new furofuran lignan glucosides, terminalosides A–K (1–4, 6–12), 2-epiterminaloside D (5), and 6-epiterminaloside K (13), were characterized using various spectroscopic techniques. Twelve of the isolates were found to contain rare tetraoxygenated aryl groups in their structures. Analysis of the NMR chemical shifts for the oxymethine signals in the furofuran ring suggested a pragmatic approach to determining the relative configuration of these compounds. The ECD and NOESY spectroscopic data obtained allowed for the deduction of the absolute configurations and conformations of the compounds. The isolates were tested for their estrogenic/antiestrogenic activity using the MCF-7 and T47D estrogen-responsive human breast cancer cell lines. Terminalosides B (2) and G (8) exhibited inhibitory effects for both cell lines, and estradiol-enhanced cell proliferation was suppressed by 90% at concentrations lower than 1...

Ryoko Izumoto

Papers

Leishmanicidal activities and cytotoxicities of bisnaphthoquinone analogues and naphthol derivatives from Burman Diospyros burmanica