0000000000210897
AUTHOR
Santina Maiorana
Development of novel 1,4-benzodiazepine-based Michael acceptors as antitrypanosomal agents
Novel 1,4-benzodiazepines, endowed with a Michael acceptor moiety, were designed taking advantage of a computational prediction of their pharmacokinetic parameters. Among all the synthesized derivatives, we identified a new lead compound (i.e., 4a), bearing a vinyl ketone warhead and endowed with a promising antitrypanosomal activity against Trypanosoma brucei brucei (IC50 = 5.29 µM), coupled with a lack of cytotoxicity towards mammalian cells (TC50>100 µM).
Drug combination studies of curcumin and genistein against rhodesain of Trypanosoma brucei rhodesiense
Curcumin and genistein are two natural products obtained from Curcuma longa L. and soybeans, endowed with many biological properties. Within the last years they were shown to possess also a promising antitrypanosomal activity. In the present paper, we investigated the activity of both curcumin and genistein against rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense; drug combination studies, according to Chou and Talalay method, allowed us to demonstrate a potent synergistic effect for the combination curcumin-genistein. As a matter of fact, with our experiments we observed that the combination index of curcumin-genistein is < 1 for the reduction from 10 to 90% of rhode…
Peptidyl Vinyl Ketone Irreversible Inhibitors of Rhodesain: Modifications of the P2 Fragment.
In this paper, we report the design, synthesis and biological investigation of a series of peptidyl vinyl ketones obtained by modifying the P2 fragment of previously reported highly potent inhibitors of rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense. Investigation of the structure-activity relationship led us to identify new rhodesain inhibitors endowed with an improved selectivity profile (a selectivity index of up to 22 000 towards the target enzyme), and/or an improved antitrypanosomal activity in the sub-micromolar range.
Drug Synergism: Studies of Combination of RK-52 and Curcumin against Rhodesain of Trypanosoma brucei rhodesiense
Rhodesain is an enzyme essential for the life of Trypanosoma brucei rhodesiense, a parasite causing a rapid-onset form of Human African Trypanosomiasis. RK-52 is a synthetic inhibitor of rhodesain,...
Evaluation of curcumin irreversibility
Dear Editor,We would like to reply to the letter to the Editor of Steverding (2018) on our research article “Drug combination studies of curcumin and genistein against rhodesain of Trypanosoma bruc...
Optimization Strategy of Novel Peptide-Based Michael Acceptors for the Treatment of Human African Trypanosomiasis
This paper describes an optimization strategy of the highly active vinyl ketone 3 which was recognized as a strong inhibitor of rhodesain of Trypanosoma brucei rhodesiense, endowed with a ksecond v...