Onyeibor, Onyeka published the artcileSynthesis of Some Cryptolepine Analogues, Assessment of Their Antimalarial and Cytotoxic Activities, and Consideration of Their Antimalarial Mode of Action, Safety of 4,5-Dichloroisatin, the main research area is cryptolepine analog preparation; antiplasmodial cytotoxic antimalarial cryptolepine analog preparation; beta hematin formation inhibition cryptolepine preparation.
A series of analogs of cryptolepine were synthesized and evaluated for their in vitro antiplasmodial and cytotoxic properties. The IC50 values of several compounds against Plasmodium falciparum (strain K1) were <0.1 μM, 5-10-fold lower than that of cryptolepine but their cytotoxicities were only 2-4 times greater than that of cryptolepine. Compounds with a halogen in the quinoline ring and a halogen or a nitro group in the indole ring have enhanced antiplasmodial activity. In mice infected with P. berghei, the 7-bromo-2-chloro and 2-bromo-7-nitro derivatives of cryptolepine suppressed parasitemia by >90% at doses of 25 mg kg-1 day-1 with no apparent toxicity to the mice. 2,7-Dibromocryptolepine was evaluated at several dose levels, and a dose-dependent suppression of parasitemia was seen (ED90 = 21.6 mg kg-1 day-1). The antimalarial mode of action of cryptolepine suppressed parasitemia by >90% at doses of 25 mg kg-1 day-1 with no apparent toxicity to the mice. appears to be similar to that of chloroquine and involves the inhibition of hemozoin formation. A number of analogs were assessed for their effects on the inhibition of β-hematin (hemozoin) formation, and the results were compared with their antiplasmodial activities having taken account of their predicted accumulation into the acidic parasite food vacuole. No correlation was seen (r2 = 0.0781) suggesting that the potent antimalarial activity of compounds such as 2,7-dibromocryptolepine involves other mechanisms in addition to the inhibition of hemozoin formation.
Journal of Medicinal Chemistry published new progress about Antimalarials. 1677-47-0 belongs to class indole-building-block, name is 4,5-Dichloroisatin, and the molecular formula is C8H3Cl2NO2, Safety of 4,5-Dichloroisatin.
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles