Synthesis and antileishmanial evaluation of thiazole orange analogs |
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| Institution: | 1. Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, USA;2. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt;3. College of Pharmacy, The Ohio State University, Columbus, OH, USA;4. Department of Chemistry, Virginia Tech, Blacksburg, VA, USA;5. Department of Chemistry, Georgia State University, Atlanta, GA, USA;1. College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, PR China;2. Institute of Botany, Jiangsu Province and Chinese Academy of Sciences (Nanjing Botanical Garden Mem. Sun Yat-Sen), 210014, PR China;3. Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing 210037, PR China;1. Institute of Natural Medicine and Green Chemistry, School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, PR China;2. School of Chemical and Environment Engineering, Wuyi University, Jiangmen 529020, PR China;3. Department of Science and Environmental Studies, Centre for Education in Environmental Sustainability, The Hong Kong Institute of Education, 10 Lo Ping Road, Tai Po, Hong Kong Special Administrative Region;1. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hněvotínská 5, 779 00 Olomouc, Czech Republic;2. Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, Lviv, 79010, Ukraine;3. Department of Public Health, Dietetics and Lifestyle Disorders, Faculty of Medicine, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland;1. School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China;2. College of Chemistry and Environmental Protection Engineering, Southwest Minzu University, Chengdu 610041, PR China;1. Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China;2. Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Guangxi Medical University, No. 22, Shuangyong Road, Nanning 530021, Guangxi, China;3. University of Chinese Academy of Sciences, Beijing 100049, China;4. School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310013, Zhejiang, China |
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| Abstract: | Cyanine compounds have previously shown excellent in vitro and promising in vivo antileishmanial efficacy, but the potential toxicity of these agents is a concern. A series of 22 analogs of thiazole orange ((Z)-1-methyl-4-((3-methylbenzod]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium salt), a commercial cyanine dye with antileishmanial activity, were synthesized in an effort to increase the selectivity of such compounds while maintaining efficacy. Cyanines possessing substitutions on the quinolinium ring system displayed potency against Leishmania donovani axenic amastigotes that differed little from the parent compound (IC50 12–42 nM), while ring disjunction analogs were both less potent and less toxic. Changes in DNA melting temperature were modest when synthetic oligonucleotides were incubated with selected analogs (ΔTm ≤ 5 °C), with ring disjunction analogs showing the least effect on this parameter. Despite the high antileishmanial potency of the target compounds, their toxicity and relatively flat SAR suggests that further information regarding the target(s) of these molecules is needed to aid their development as antileishmanials. |
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| Keywords: | Leishmaniasis Drug discovery Cyanine |
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