Results in Chemistry of Natural Organic Compounds. Synthesis of New Anticancer Vinca Alkaloids and Flavone Alkaloids

The antitumor indole–indoline alkaloids of the evergreen Catharanthus roseus—namely vinblastine and vincristine—are widely used in chemotherapy of cancer. Many efforts were made to synthesize more efficient derivatives with less side-effect. The 14,15-cyclopropane derivative of vinblastine was synthesized successfully by a five-step procedure starting from vindoline. Vincristine, vinorelbine and several derivatives condensed with a cyclopropane ring were synthesized. Various hybrid molecules were prepared by the coupling reaction of vindoline and methyl ester of tryptophan, which were conjugated by carrier peptides of octaarginine. Studying the halogenation reactions of vindoline and catharanthine some fluorine derivatives were obtained which showed promising antitumor activity on various tumor types. The synthesis of the Aspidospermane alkaloid bannucine and 5′-epibannucine were carried out using N-acyliminium intermediates. The same intermediate was also applied in the first synthesis of sessiline. The research group have synthesized of flavonoid alkaloids: dracocephins A and B. Further three flavonoid alkaloids, namely 8-(2”-pyrrolidinon-5′′-yl)quercetin, 6-(2′′-pyrrolidinon-5′′-yl)-(−)- and 8-(2′′-pyrrolidinon-5′′-yl)-(−)-epicatechin were prepared by acid-catalyzed regioselective Mannich reaction starting from the corresponding flavonoid precursor. Vindoline was also coupled to synthetic pharmacophores, such as triphenylphosphine and various N-heterocycles. Some of these hybrid molecules showed significant antitumor activity. Furthermore, 7-OH and 7-NH modified flavonoid derivatives were synthesized by a regioselective alkylation followed by Smiles rearrangement and hydrolysis.

A STUDY ON DIFFERENT PLANTS OF APOCYNACEAE FAMILY AND THEIR MEDICINAL USES

The apocynaceae family is one of the most medicinally diverse families in the plant kingdom and is a rich source for drugs that have found use both traditionally and in conventional medicine. The medicinal activity of these plants was due to the presence of alkaloids which were either indoline alkaloids or steroidal alkaloids. The family Apocynaceae consists of tropical trees, shrubs and vines. Characteristic features of the family are that almost all species produce milky sap. In traditional medicine, Apocynaceae species are used to treat gastrointestinal ailments, fever, malaria, pain and diabetes, including skin and ecto-parasitic diseases. Some are important timber species while many are planted as ornamentals. Non-medicinal uses include food, poisons, fodder, wood, ornamentals, dye and perfume. A total of 4600 species under 415 genera belonging to the family Apocynaceae were collected and identified. Species of Apocynaceae have been reported to possess anticancer and antimalarial properties. Species having cytotoxic activity include those of Catharanthus, Nerium, Plumeria, Tabernaemontana and Ichnocarpus. Catharanthusroseus is the most medicinally important plant in this family due to its use in the treatment of various types of cancers, other agents that have been derived from this family include the alkaloids reserpine and rescinamine which have been used against hypertension, others are the cardiac glycosides.