Search results for: SW41
#32686409 
2020/07/20
To Up
An Antiparasitic Compound from the Medicines for Malaria Venture Pathogen Box Promotes Tubulin Polymerization.
The few frontline antileishmanial drugs are poorly effective and toxic. To search for new drugs for this neglected tropical disease, we tested the activity of compounds in the Medicines for Malaria Venture (MMV) "Pathogen Box" against axenic amastigotes. Screening yielded six discovery antileishmanial compounds with EC values from 50 to 480 nM. Concentration-response assays demonstrated that the best hit, MMV676477, had mid-nanomolar cytocidal potency against intracellular amastigotes, , and , suggesting broad antiparasitic activity. We explored structure-activity relationships (SAR) within a small group of MMV676477 analogs and observed a wide potency range (20-5000 nM) against axenic amastigotes. Compared to MMV676477, our most potent analog, SW41, had ∼5-fold improved antileishmanial potency. Multiple lines of evidence suggest that MMV676477 selectively disrupts tubulin dynamics. Morphological studies indicated that MMV676477 and analogs affected during cell division. Differential centrifugation showed that MMV676477 promoted partitioning of cellular tubulin toward the polymeric form in parasites. Turbidity assays with purified and porcine tubulin demonstrated that MMV676477 promoted leishmanial tubulin polymerization in a concentration-dependent manner. Analogs' antiparasitic activity correlated with their ability to facilitate purified tubulin polymerization. Chemical cross-linking demonstrated binding of the MMV676477 scaffold to purified tubulin, and competition studies established a correlation between binding and antileishmanial activity. Our studies demonstrate that MMV676477 is a potent antiparasitic compound that preferentially promotes microtubule polymerization. Due to its selectivity for and broad-spectrum activity against multiple parasites, this scaffold shows promise for antiparasitic drug development.Imran Ullah, Suraksha Gahalawat, Laela M Booshehri, Hanspeter Niederstrasser, Shreoshi Majumdar, Christopher Leija, James M Bradford, Bin Hu, Joseph M Ready, Dawn M Wetzel
2096 related Products with: An Antiparasitic Compound from the Medicines for Malaria Venture Pathogen Box Promotes Tubulin Polymerization.
100ug100ug Lyophilized 100ul100ug0.1 mg500 100ug100ug100μg 25 100ug Lyophilized
Related Pathways
#30395292 2018/11/01
To Up
Characterization of a Lipase From the Silkworm Intestinal Bacterium Bacillus pumilus With Antiviral Activity Against Bombyx mori (Lepidoptera: Bombycidae) Nucleopolyhedrovirus In Vitro.
To investigate whether Bombyx mori Linnaeus (Lepidoptera: Bombycidae) intestinal microorganism play a role in the host defence system against viral pathogens, a lipase gene from the silkworm intestinal bacterium Bacillus pumilus SW41 was characterized, and antiviral activity of its protein against B. mori nucleopolyhedrovirus (BmNPV) was tested. The lipase gene has an open-reading frame of 648 bp, which encodes a 215-amino-acid enzyme with a 34-amino-acid signal peptide. The recombinant lipase (without signal peptide) was expressed and purified by using an Escherichia coli BL21 (DE3) expression system. The total enzyme activity of this recombinant lipase reached 277.40 U/mg at the optimum temperature of 25°C and optimum pH value of 8.0. The antiviral test showed that a relative high concentration of the recombinant lipase reduced BmNPV infectivity in vitro, which resulted in decreased viral DNA abundance and viral occlusion bodies. Besides, the preincubation method also suggested that the lipase probably directly acting on the budded virions. The results suggest that the lipase from intestinal bacterium B. pumilus SW41 is a potential antiviral factor for silkworm against BmNPV.Renhua Liu, Wenhui Wang, Xiaoyuan Liu, Yan Lu, Tingting Xiang, Wei Zhou, Yongji Wan