In search of new leads: A closer look at the therapeutic potential of the constituents of millettia thonningii, Millettia pachycarpa and their structural analogues

Abstract

This review discusses the potential applications of isoflavonoids from Millettia thonningii and M. pachycarpa in developing new pharmaceutical agents based on folkloric anecdotes and evidences from pharmacological and biochemical assays and to encourage further research into their pharmacological applications. Millettia thonningii is a deciduous plant indigenous to tropical West Africa, M. pachycarpa, is a climbing shrub indigenous to South-East Asia and other species have been used in folk-medicine for the treatment of inflammatory diseases, chronic diseases and several pathogenic diseases. Scientific research has implicated several prenylated isoflavonoids as being useful antioxidants and used in the management of radical-mediated diseases such as cancer, diabetes, ischemic heart diseases, Alzheimer's and Parkinson's diseases etc. Chemical investigations into these plants have revealed that they contain several isoflavonoids which bear structural resemblance to some of the isoflavonoids already in allopathic medical usage. Plants continue to maintain their historical stead as a store house of important drug candidates and source of new "leads" for synthetic modifications to improve activity through optimization of pharmacodynamic and pharmacokinetic properties. Natural products have also been found useful in specific pharmacological probes, a potential which is grossly underestimated. The alpinumisoflavones which have been isolated from the Millettia thonningii have shown high toxicities to the brine shrimp while isolates from M. pachycarpa have also shown anti-estrogenic and anticancer properties. Information obtained from crystal structural studies of these alpinumisoflavonoids coupled with their molecular and electronic distribution properties can further our understanding of their therapeutic potential and their observed bioactivities. The alpinumisoflavones are characterized by a fused tricyclic ring system which contains nearly coplanar benzopyrone ring fragments and a puckered six membered pyran ring that adopts a half-chair conformation with inter and intra molecular O-H....O and C-H...O contacts. A phenyl ring attached to the benzopyrone moiety shows out of plane twist with various degrees of torsion depending on the substitution on the phenyl ring.