Repurposing Drugs for Tropical Diseases: Case Studies and Open‐Source Screening Initiatives

Chong, Curtis R.

doi:10.1002/9781118274408.ch11

Cited by 2 publications

(2 citation statements)

References 245 publications

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“…In the last few years, we have witnessed more and more collaborations between academia and drug industry. For example, big pharmaceutical companies like Glaxo-SmithKline, Genentech, Merck, Abbott, Pfizer, Novartis, AstraZeneca and Eli Lilly provided information of their proprietary compounds for drug repurposing [11]. More recently, scientists called for the release of patient-level clinical trial data to benefit the drug discovery by increasing efficiency of drug development and reducing the duplication of efforts [12].…”

Section: Collaboration Is the Trendmentioning

confidence: 99%

Computational Target Fishing: What Should Chemogenomics Researchers Expect for the Future of in silico Drug Design and Discovery?

Wang

Xie

2014

Future Med. Chem.

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Section: Collaboration Is the Trendmentioning

confidence: 99%

Computational Target Fishing: What Should Chemogenomics Researchers Expect for the Future of in silico Drug Design and Discovery?

Wang

Xie

2014

Future Med. Chem.

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“…To make matters worse, the isolates resistant to antimonials or miltefosine showed improved fitness (6,7). In the short term, liposomal preparations of amphotericin B, combination therapy (8), and drug repurposing (9) constitute the core treatments for confronting this alarming situation. Nevertheless, in the long term, the development of new leads is mandatory in order to hasten their optimization and further implementation.…”

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confidence: 99%

Mechanisms of Action of Substituted β-Amino Alkanols on Leishmania donovani

Abengózar

Bustos

García-Hernández

et al. 2015

Antimicrob Agents Chemother

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Leishmaniasis is the protozoan disease second in importance for human health, superseded only by malaria; however, the options for chemotherapeutic treatment are increasingly limited due to drug resistance and toxicity. Under this perspective, a quest for new chemical compounds is urgently needed. An N-substituted 2-aminoalkan-1-ol scaffold has been shown to be a versatile scaffold for antiparasitic activity. Knowledge about its mechanism of action is still rather limited. In this work, we endeavored to define the leishmanicidal profile of such ␤-amino alkanol derivatives using a set of 15 N-mono-and disubstituted surrogates, tested on Leishmania donovani promastigotes and intracellular amastigotes. The best compound (compound 5), 2-ethylaminododecan-1-ol, had a 50% effective concentration (EC 50 ) of 0.3 M and a selectivity index of 72 for infected THP-1 cells and was selected for further elucidation of its leishmanicidal mechanism. It induced fast depletion of intracellular ATP content in promastigotes in the absence of vital dye intracellular entry, ruling out plasma membrane permeabilization as its origin. Confocal and transmission electron microscopy analyses showed that compound 5 induced severe mitochondrial swelling and vesiculation. Polarographic analysis using an oxygen electrode demonstrated that complex II of the respiratory chain (succinate reductase) was strongly inhibited by compound 5, identifying this complex as one of the primary targets. Furthermore, for other ␤-amino alkanols whose structures differed subtly from that of compound 5, plasma membrane permeabilization or interference with membrane traffic was also observed. In all, N-substituted ␤-amino alkanols were shown as appealing leishmanicidal candidates deserving further exploration.

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Repurposing Drugs for Tropical Diseases: Case Studies and Open‐Source Screening Initiatives

Cited by 2 publications

References 245 publications

Computational Target Fishing: What Should Chemogenomics Researchers Expect for the Future of in silico Drug Design and Discovery?

Computational Target Fishing: What Should Chemogenomics Researchers Expect for the Future of in silico Drug Design and Discovery?

Mechanisms of Action of Substituted β-Amino Alkanols on Leishmania donovani

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