Combating Malaria with Plant Molecules: A Brief Update

Abstract

Observations on the role of ovarian hormones in breast cancer growth, as well as interest in contraception, stimulated research into the biology of estrogens. The identification of the classical receptors ERα and ERβ and the transmembrane receptor GPER and the resolution of the structure of the ligand bound to its receptor established the principal molecular mechanisms of estrogen action. The presence of estrogen-like compounds in many plants used in traditional medicine or ingested as food ingredients, phytoestrogens, as well as the estrogenic activities of many industrial pollutants and pesticides, xenoestrogens, have prompted investigations into their role in human health. Phyto- and xenoestrogens bind to the estrogen receptors with a lower affinity than the endogenous estrogens and can compete or substitute the hormone. Xenoestrogens, which accumulate in the body throughout life, are believed to increase breast cancer risk, especially in cases of prenatal and prepuberal exposure whereas the role of phytoestrogens is still a matter of debate. At present, the application of phytoestrogens appears to be limited to the treatment of post-menopausal symptoms in women where the production of endogenous estrogens has ceased. In this review we discuss chemistry, structure and classification, estrogen signaling and the consequences of the interactions of estrogens, phytoestrogens and xenoestrogens with their receptors, the complex interactions of endogenous and exogenous ligands, the evaluation of the health risks related to xenoestrogens, and the perspectives toward the synthesis of potent third generation selective estrogen receptor modulators (SERMs).

Natural Products as Pharmaceuticals and Sources for Lead Structures**Note: This chapter reflects the opinions of the authors, not necessarily those of the US Government

“…The alkaloid quinine ( Figure 5.18), isolated from the bark of the South American tree Cinchona officinalis and other trees of the same genus, was the first effective antimalarial agent to be discovered, and it has been called "the drug to have relieved more human suffering than any other in history" [258]. The alkaloid quinine ( Figure 5.18), isolated from the bark of the South American tree Cinchona officinalis and other trees of the same genus, was the first effective antimalarial agent to be discovered, and it has been called "the drug to have relieved more human suffering than any other in history" [258].…”

“…The importance of artemisinin has led to several synthetic and semisynthetic approaches to its production to complement its isolation from A. annua. Other potential antimalarial natural products are described in two recent reviews [258,268]. Many analogues and derivatives of artemisinin have been prepared in attempts to improve its activity and utility.…”

Antimalarial activity of Curcuma caesia against 3D7 and K1 strains of Plasmodium falciparum

“…As an example quinine from Cinchona, and artemisinin isolated from Qinghaosu [3]. Many recent studies concentrate on natural and herbal product in search of antimalarial drugs [4,5]. caesia is one of the traditional tribal medicinal plants which is used in India for treatment of fever and other ailments.…”

Synthesis and biological characterisation of ester and amide derivatives of fusidic acid as antiplasmodial agents

“…Two of the most effective antimalarial drugs quinine and artemisinin are natural products isolated from Cinchona officinalis and Artemisia annua, respectively, and many of the synthetic antimalarial drugs are analogues of these two natural products. [5][6][7][8] Fusidic acid (FA) ( Figure 1) is a steroid-based, narrow spectrum bacteriostatic antibiotic belonging to a family of naturally occurring antibiotics, the fusidanes, which have a tetracyclic ring system with a unique chair-boat-chair proposed to be through inhibition of plasmodial EF-Gs, which harbour bacteria-like metabolic processes and are localised within the parasite's mitochondria and the relict apicoplast.…”