quinine and tetrandrine

Cancer is a prominent cause of death globally. Currently, many drugs that are in clinical practice are having a high prevalence of side effect and multidrug resistance. Risk of tumors acquiring resistance to chemotherapy (multidrug resistance) remains a significant hurdle to the successful treatment of various types of cancer. Membrane-embedded drug transporters, generally overexpressed in cancer, are the leading cause among multiple mechanisms of multidrug resistance (MDR). P-glycoprotein (P-gp) also MDR1/ABCB1, multidrug resistance associated protein 1 (MRP1/ABCC1), MRP2 and breast cancer resistance protein (BCRP/ABCG2) are considered to be a prime factor for induction of MDR. To date, several chemical substances have been tested in a number of clinical trials for their MDR modulatory activity which are not having devoid of any side effects that necessitates to find newer and safer way to tackle the current problem of multidrug resistance in cancer. The present study systematically discusses the various classes of natural products i.e flavonoids, alkaloids, terpenoids, coumarins (from plants, marine, and microorganisms) as potential MDR modulators and/or as a source of promising lead compounds. Recently a bisbenzyl isoquinoline alkaloid namely tetrandrine, isolated from Chinese herb Stephania tetrandra (Han-Fang-Chi) is in clinical trials for its MDR reversal activity.

Topics: Alkaloids; Animals; Antineoplastic Agents; ATP-Binding Cassette Transporters; Benzylisoquinolines; Biological Products; Cell Line, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Flavonoids; Humans; Terpenes

An alkaloid extract derived from the roots of Cyclea barbata demonstrated cytotoxic and antimalarial activities, and five bisbenzylisoquinoline alkaloids, (+)-tetrandrine [1], (-)-limacine [2], (+)-thalrugosine [3], (+)-homoaromoline [4], and (-)-cycleapeltine [5], were isolated as the active principles. The complete and unambiguous assignments of the 1H- and 13C-nmr data of these substances were made by 1D and 2D nmr techniques (COSY, phase-sensitive ROESY, HETCOR, and FLOCK).

Topics: Alkaloids; Animals; Antimalarials; Antineoplastic Agents, Phytogenic; Asia; Benzylisoquinolines; Cell Survival; Drug Screening Assays, Antitumor; Erythrocytes; Humans; In Vitro Techniques; KB Cells; Leukemia P388; Magnetic Resonance Spectroscopy; Plants, Medicinal; Plasmodium falciparum; Spectrophotometry, Ultraviolet; Tumor Cells, Cultured