New Antimalarial Drug Discovery in India and Future Strategy for Malaria Control

G P Dutta

G P Dutta Ex-Director’s Grade Scientist-G and CSIR Emeritus Scientist, CSIR-Central Drug Research Institute, Lucknow

Keywords: Antimalarial, Drug Discovery, Blood Schizontocidal, Artemisinins, Plasmodium yielii nigeriensis (MDR), Malaria Eradication, Transmission Blocking

Abstract

This INSA commissioned report on “New antimalarial drug discovery in India and future strategy for malaria control” focuses on development of : (A) new fast-acting blood schizontocides which could (1) control the multidrug resistant
strains of Plasmodium falciparum/P. vivax, (2) reduce high malaria related mortality among complicated/comatose cerebral malaria cases, and (3) save children dying due to severe malaria; (B) safe anti-relapse (Radical Curative) drugs for P. vivax/ P. ovale, to replace toxic primaquine (which is the only drug in clinical use for the last six decades); (C) new Transmission Blocking Drugs which prevent the spread of multidrug resistant P. falciparum: primaquine is the only transmission blocking drug that sterilizes gametocytes in man (vertebrate host) and thus interrupts transmission of P. falciparum but which is
contraindicated for infants, children and pregnant women and G-6-PD deficient red cell cases by World Health Organization Safety Committees; (D) safe 8-aminoquinolines (to replace primaquine) which do not cause methaemoglobinaemia, cyanosis, hemolytic anaemia; (E) effective antimalarials for emerging artemisinin resistance/MDR strains of P. falciparum and P.vivax; (F) a safe antimalarial drug for pregnancy, and (G) a safe effective ACT drug combination for control of uncomplicated/MDR P. falciparum infections. During the past five years, nearly 32 Malaria Eradication Agenda sponsored by International Malaria Experts have expressed that the present armamentarium may not achieve malaria eradication or prevent malaria
related mortality because of lack of effective antimalarials. CSIR-Central Drug Research Institute has developed the following new antimalarials which will be helpful to achieve some of the malarial control/eradication objectives: (a) Fast-
Acting Blood Schizontocides like a/b-Arteether (patented 1990), a-Arteether, b-Arteether (in groundnut oil), Dihydroartemisinin (patented Internationally in Sixteen Countries, 1999 and 2000), Dihydroartemisinin and Piperaquine
(ACT approved by WHO 2010), a/b-artelinate (patented in 1989), Pyronaridine (2000), Synthetic 1,2,4-Trioxanes (Fenozan), Azithromycin, Tafenoquine (a broad spectrum antimalarial) (jointly developed by WRAIR and CDRI 1988); (b) New Leads for Gametocytocidal Drugs: Artemisinin which kills P. cynomolgi B gametocytes in anopheles mosquitoes (1989), a/b-Arteether as intra-muscular (single) or oral dose for P. cynomolgi B. (1990, 1996), Sod. b-artelinate (1996); (c) New Safe Leads: gametocytocidal/transmission blocking drugs Tafenoquine (WR 238605), Bulaquine (CDRI 80/53) (2005) gametocytocidal for P. falciparum; (d) New Anti-Relapse Drugs (Hypnozoiticidal) as safe substitutes for Primaquine: CDRI 80/53/Elubaquine/Bulaquine (1989, patented), Aablaquine (Bulaquine + Chloroquine) (patented, 2000), Tafenoquine (WR 236805, 1988); (e) New Causal Prophylactic Drugs: Bulaquine (Elubaquine), Tafenoquine (WR 238605) and (f) Rectal Suppositories as Pre-Referal Emergency Treatment for children suffering from severe malaria/cerebral malaria: a/b-Arteether (CDRI-CIMAP Joint Patent 2001), Dihydroartemisinin (CDRI-CIMAP Joint Patent 1999 and 2000).