[The search for new antiparasitic agents. 10. The synthesis, toxicological and antimalarial properties of nitrogen-containing heterocycles with a 4-(4-alkylpiperazinyl-1) phenylamine substituent (the preparation quinoprazine)]. / Izyskanie novykh protivoparazitarnykh sredstv. 10. Sintez, toksikologicheskkie i protivomaliariinye svoistva nekotorykh azotsoderzhashchikh geterotsiklov s 4-(4-alkilpiperazinil-1)fenilaminnym zamestitelem (preparat khinoprazin).

Synthesis is described and acute toxicity and antimalaria action is studied in new derivatives of quinoline and benzo(g)quinoline containing a 4-(4-alkylpiperazinyl-1)phenylamine substitute. Only the derivatives of benzo(g)quinoline were found to have a high antimalaria effect and to have advantages over the standard agent chloroquine on their tolerance and protective action. One of the compounds, 4-[4-(4-ethylpiperazinyl-1)phenylamino] benzo(g)quinoline, named QUINOPRAZINE, showed some action against Plasmodium berghei chloroquine--resistant infection (isolate LN-K65). This agent was elected for further tests.

[The modelling of the multiple drug resistance of the malarial parasites. 1. The combined resistance of Plasmodium berghei to chloroquine and fansidar]. / Modelirovanie mnozhestvennoi lekarstvennoi ustoichivosti maliariinykh parazitov. Soobshchenie 1. Sochetannaia ustoichivost' Plasmodium berghei k khlorokhinu i fansidaru.

Using a recurrent technique, P. berghei isolate resistant to chloroquine-fansidar combination is formed in golden hamsters. The isolate resistant to chloroquine-fansidar combination was 4 times less sensitive to chloroquine, 2 times less sensitive to fansidar and its combinations, 2 times less sensitive to sulfadoxine, 31 times less sensitive to pyrimethamine, as compared to the baseline isolate LNK65 P. berghei characterized by naturally reduced sensitivity to chloroquine.

[Drug resistance of malarial parasites and the methods for its determination]. / Lekarstvennaia ustoichivost' maliariinykh parazitov i metody ee opredeleniia.

The problem of drug resistance of Plasmodium falciparum, the causative agent of tropical malaria and its role in the general system of malaria control are discussed. The aspects of distribution of drug resistant strains of P. falciparum and the main principles of determination of the malaria causative agent sensitivity to antimalaria drugs are presented. The determination implies the use of various procedures for performing the tests under clinical conditions in vivo and various modifications of the in vitro tests, as well as estimation of their results. The use of a 48-hour in vitro test provided the revealing of certain advantages of dabequine, a new drug made in the USSR in comparison to chloroquine with respect to drug resistant strains of P. falciparum from the southern areas of Vietnam. The advantages and disadvantages or limitations of every procedure in comparison to the others are indicated and it is shown that the in vivo and in vitro tests are supplementing each other. The known procedures provide the results not earlier than in 24-48 hours which required developing of a rapid procedure. Brief characteristics of a rapid biochemical procedure are presented. This procedure was developed at the E. I. Martsinovsky Institute of Medical Parasitology and Tropical Medicine on an experimental model of P. berghei, the causative agent of rodent malaria. It provides the results in 4-5 hours.