Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) a... more Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (-)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (-)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ cau...
Clear and rational thinking: A series of rationally designed, lansine-derived carbazoles was synt... more Clear and rational thinking: A series of rationally designed, lansine-derived carbazoles was synthesized and evaluated for activity against promastigotes and amastigotes of Leishmania donovani, the causative agent of leishmaniasis. Some structural modifications gave rise to compounds with enhanced activity and selectivity over lansine, allowing structure-activity relationships to be elucidated and providing a foundation for the further development of this pharmacophore.
Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) a... more Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (-)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (-)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ cau...
In our study, the inhibitory activity of curcuminoids towards Plasmodium falciparum thioredoxin r... more In our study, the inhibitory activity of curcuminoids towards Plasmodium falciparum thioredoxin reductase (PfTrxR) was determined using LC-MS-based functional assay and showed that only demethoxycurcumin (DMC) inhibited PfTrxR (IC50: 2 μM). In silico molecular modelling was used to ascertain and further confirm that the binding affinities of curcumin and DMC are towards the dimer interface of PfTrxR. The in vitro antiplasmodial activities of curcumin and DMC were evaluated and shown to be active against chloroquine (CQ)-sensitive (D6 clone) and moderately active against CQ-resistant (W2 clone) strains of Plasmodium falciparum while no cytotoxicity was observed against Vero cells.
Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) a... more Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (-)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (-)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ cau...
Clear and rational thinking: A series of rationally designed, lansine-derived carbazoles was synt... more Clear and rational thinking: A series of rationally designed, lansine-derived carbazoles was synthesized and evaluated for activity against promastigotes and amastigotes of Leishmania donovani, the causative agent of leishmaniasis. Some structural modifications gave rise to compounds with enhanced activity and selectivity over lansine, allowing structure-activity relationships to be elucidated and providing a foundation for the further development of this pharmacophore.
Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) a... more Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (-)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (-)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ cau...
In our study, the inhibitory activity of curcuminoids towards Plasmodium falciparum thioredoxin r... more In our study, the inhibitory activity of curcuminoids towards Plasmodium falciparum thioredoxin reductase (PfTrxR) was determined using LC-MS-based functional assay and showed that only demethoxycurcumin (DMC) inhibited PfTrxR (IC50: 2 μM). In silico molecular modelling was used to ascertain and further confirm that the binding affinities of curcumin and DMC are towards the dimer interface of PfTrxR. The in vitro antiplasmodial activities of curcumin and DMC were evaluated and shown to be active against chloroquine (CQ)-sensitive (D6 clone) and moderately active against CQ-resistant (W2 clone) strains of Plasmodium falciparum while no cytotoxicity was observed against Vero cells.
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Papers by Rajnish Sahu