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<p>African trypanosomiasis is a major health threat to humans and animals in 36 countries within sub-Saharan Africa. We previously identified quinolone hydrazides exhibiting sub-micromolar anti-trypanosomal activity. However, the most potent compounds had poor aqueous solubility of &lt;5 µM, hindering advancement to efficacy studies in animals. Accordingly, we generated a series of nine quinolone hydrazide analogues and evaluated in vitro anti-trypanosomal activity, cell toxicity and selected physicochemical properties. Compounds <b>4</b> and <b>5</b>, exhibited potent anti-trypanosomal activity of 0.362 ± 0060 µM and 1.251 ± 0.295 µM, respectively and showed no toxicity (CC<sub>50</sub> &gt; 20 µM) against HEK 293 cells. The two compounds showed slightly improved aqueous solubility of 5 µM when compared to the previously identified lead compounds and good LogD values (2–3).</p><p></p>

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Synthesis and in vitro anti-trypanosomal evaluation of quinolone hydrazide analogues

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月1日

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  • Phelelisiwe S. Dube,
  • Sarah Makgoba,
  • Karol R. Francisco,
  • Lesetja J. Legoabe,
  • Conor R. Caffrey,
  • Richard M. Beteck

摘要

African trypanosomiasis is a major health threat to humans and animals in 36 countries within sub-Saharan Africa. We previously identified quinolone hydrazides exhibiting sub-micromolar anti-trypanosomal activity. However, the most potent compounds had poor aqueous solubility of <5 µM, hindering advancement to efficacy studies in animals. Accordingly, we generated a series of nine quinolone hydrazide analogues and evaluated in vitro anti-trypanosomal activity, cell toxicity and selected physicochemical properties. Compounds 4 and 5, exhibited potent anti-trypanosomal activity of 0.362 ± 0060 µM and 1.251 ± 0.295 µM, respectively and showed no toxicity (CC50 > 20 µM) against HEK 293 cells. The two compounds showed slightly improved aqueous solubility of 5 µM when compared to the previously identified lead compounds and good LogD values (2–3).