Chapter 10 - Alkaloids From Apocynaceae: Origin, Pharmacotherapeutic Properties, and Structure-Activity Studies

Abstract

Abstract Alkaloids are a diverse group of naturally occurring secondary compounds derived from amino acids or the process of transamination. Some synthetic compounds with similar structure are also called alkaloids. Alkaloids provide useful starting templates for new drug designing. The botanical family Apocynaceae (also known as Dogbane family) consists of almost 250 genera and 2000 species of plants of various habits. Apocynaceae is especially rich in bioactive alkaloids such as reserpine, ajmaline, ajmalicine, yohimbine, serpentine, deserpine, thevetin, oleanderin, vincristine, vinblastine, catharanthine, vindoline, tabernanthine, tabernaemontanine, ibogamine, neriifolin, neriocorin, echitamine, alstonine, and many more with biological and therapeutic significance. Alkaloids are significantly abundant in the genera Rauvolfia, Catharanthus, Alstonia, Tabernaemontana, Strophanthus etc. Indole, bisindole, terpenoid indole, β-carboline indole, monomeric indole, acridone, pregnane, and steroidal are the various types and subtypes of alkaloids isolated from the apocynaceous plants. The Catharanthus (Vinca) alkaloids consist of a group of almost 130 terpenoid indole alkaloids of high medicinal significance of which vinblastine has been marketed for about 50 years as an anticancer therapeutic and a true lead for anticancer drug discovery. Besides, Vinca alkaloids have also been used as hypoglycemic, against high blood pressure and as disinfectants. The antihypertensive indole alkaloid reserpine from the genus Rauvolfia has also exhibited profound activity against cancer cell lines. Since medicinal plants produce a number of secondary metabolites with curative properties, alkaloids are no exception in this regard. Plant alkaloids have exhibited diverse pharmacological and medicinal properties such as antihypertensive, cytotoxic, anti-inflammatory, vasorelaxant, uterotrophic, antiparasitic, antimicrobial, opioid analgesic, antifertility, antidiabetic, neuroprotective, acetylcholinesterase inhibitiory, inducible nitric oxide synthase inhibitory, muscle relaxation, and antitussive activities. Many of these alkaloids are also used in cancer chemotherapy. Bioactivity-guided isolation has led to characterization of alkaloid rich antipsychotic and cytotoxic constituents from Apocynaceae members. Unfortunately, little is known about the underlying mechanism of bioactivity, and very little systematic structure-activity relationship studies have been undertaken in this diverse class of natural product. Synergistic effects among closely related compounds may serve as a crucial factor in determining pharmacological properties of plant constituents. Therefore, information on structure-bioactivity relationships of alkaloids and their naturally occurring congeners and semisynthetic derivatives is of immense importance in facilitating rational designing of novel drugs based on leads from natural alkaloids. This review is focused on the origin, analysis of the pharmacological and medicinal properties, and structural significance of bioactivities exerted by the plant-derived alkaloids. Moreover, to unfold future research openings, lacunae in the present understanding are also highlighted. Together, this review may further direct to the synthetic optimization of alkaloid as lead compound for the development of efficacious and clinically applicable alkaloid analogues.