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Mode of Action Studies on New Compounds with Leishmanicidal Activity, Through Functional Genomics Approach

ABSTRACT: Mode of Action Studies on New Compounds with Leishmanicidal Activity, Through Functional Genomics Approach

PROVIDER: PRJNA1000525 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25469945_1.fastq.gz	Fastqsanger.gz
	SRR25469945_2.fastq.gz	Fastqsanger.gz
	SRR25469946_1.fastq.gz	Fastqsanger.gz
	SRR25469946_2.fastq.gz	Fastqsanger.gz
	SRR25469947_1.fastq.gz	Fastqsanger.gz

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Mode of Action Studies on New Compounds with Leishmanicidal Activity, Through Functional Genomics Approach

Project description:Leishmaniasis affects mainly the poorest population of the third world. Among visceral and cutaneous leishmaniasis (VL and CL, respectively), visceral leishmaniasis is the deadliest parasitic disease. There are no vaccines against leishmaniasis and the chemotherapeutic agents currently used are also insufficient. Pentavalent antimonials are being used for the effective treatment of Leishmaniasis. In this study, we characterized compounds with leishmanicidal activity, and determined its mode of action through the whole transcriptome analyiss. The Lesihmania strains were treated with previously identified selected anti-leishmanial compounds in promastigotes cultures on M199 medium (supplemented with L-glutamine, 10% heat-inactivated fetal bovine serum, 0.25% hemin, 40 mM NaHCO3, 100μM adenine, 40 mM HEPES, 100 U/mL penicillin and 100μg/mL streptomycin). Following the total RNA isolation, RNA-seq was performed using the Illumina NextSeq500 system. The genes expression profiling in the treated and control samples were determined using the standard bioinormatics tools, and then compared statistically.

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Mode of action studies for a novel anti-leishmania compound

Project description:We describe the development of a novel anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound is efficacious in a mouse model of visceral leishmaniasis, and has suitable physicochemical, pharmacokinetic and toxicological properties for further development and has been declared a preclinical candidate. Detailed mode of action studies indicate that compounds from this series act principally by inhibiting the parasite protein kinases.

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Project description:This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/The drug Praziquantel is the most commonly used drug for parasitic flatworms. It is currently being increasingly used in mass drug administration programmes, raising concerns over whether resistance will develop. Although widely used, its mode of action was until very recently uncertain. This study will investigate the praziquantel mode of action and resistance by sequencing the transcriptomes of Dugesia japonica and different stages and strains of S. mansoni.

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