Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae

• Main Authors: Ruqaiyyah Siddiqui (Author), Mohammed I. El-Gamal (Author), Anania Boghossian (Author), Balsam Qubais Saeed (Author), Chang-Hyun Oh (Author), Mohammed S. Abdel-Maksoud (Author), Ahmad M. Alharbi (Author), Hasan Alfahemi (Author), Naveed Ahmed Khan (Author)
• Format: Book
• Published: MDPI AG, 2022-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<i>Naegleria fowleri (N. fowleri)</i> is a free-living, unicellular, opportunistic protist responsible for the fatal central nervous system infection, primary amoebic meningoencephalitis (PAM). Given the increase in temperatures due to global warming and climate change, it is estimated that the cases of PAM are on the rise. However, there is a current lack of awareness and effective drugs, meaning there is an urgent need to develop new therapeutic drugs. In this study, the target compounds were synthesized and tested for their anti-amoebic properties against <i>N. fowleri.</i> Most compounds exhibited significant amoebicidal effects against <i>N. fowleri</i>; for example, <b>1h</b>, <b>1j</b>, and <b>1q</b> reduced <i>N. fowleri's</i> viability to 15.14%, 17.45% and 28.78%, respectively. Furthermore, the majority of the compounds showed reductions in amoeba-mediated host death. Of interest are the compounds <b>1f</b>, <b>1k</b>, and <b>1v</b>, as they were capable of reducing the amoeba-mediated host cell death to 52.3%, 51%, and 56.9% from 100%, respectively. Additionally, these compounds exhibit amoebicidal properties as well; they were found to decrease <i>N. fowleri's</i> viability to 26.41%, 27.39%, and 24.13% from 100%, respectively. Moreover, the MIC₅₀ values for <b>1e</b>, <b>1f</b>, and <b>1h</b> were determined to be 48.45 µM, 60.87 µM, and 50.96 µM, respectively. Additionally, the majority of compounds were found to exhibit limited cytotoxicity, except for <b>1l</b>, <b>1o</b>, <b>1p</b>, <b>1m</b>, <b>1c</b>, <b>1b</b>, <b>1zb</b>, <b>1z</b>, <b>1y</b>, and <b>1x</b>, which exhibited negligible toxicity. It is anticipated that these compounds may be developed further as effective treatments against these devastating infections due to brain-eating amoebae.

Item Description

10.3390/antibiotics11111515
2079-6382