Synthesis and Comparison of In Vitro Leishmanicidal Activity of 5-(Nitroheteroaryl)-1, 3, 4-Thiadiazols Containing Cyclic Amine of Piperidin-4-ol at C-2 with Acyclic Amine Analogues against Iranian Strain of Leishmania major (MRHO/IR/75/ER)

Tehran University of Medical Sciences Journal of Arthropod-Borne Diseases 2322-1984 11 1 2017 04 18 Synthesis and Comparison of In Vitro Leishmanicidal Activity of 5-(Nitroheteroaryl)-1, 3, 4-Thiadiazols Containing Cyclic Amine of Piperidin-4-ol at C-2 with Acyclic Amine Analogues against Iranian Strain of Leishmania major (MRHO/IR/75/ER) 95 104 EN Azar Tahghighi Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran AND Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran Alireza Foroumadi Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran Susan Kabudanian Ardestani Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran Seyed Mohammad Amin Mahdian Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran 2016 05 28 2016 05 28 Background: Cutaneous Leishmaniasis (CL) is endemic in many tropical and subtropical regions of the world. Due to the prolonged duration of therapy, adverse effect and resistance to current drugs in the treatment of CL, the discovery of novel, efficient, and safe leishmanicidal drugs is required. The aims of the present study was to synthesis of new compounds based on the active compounds of 5-(5-nitrofuran-2-yl)- and 5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazole bearing the linear amino alcohol of 3-aminopropan-1-ol in the C-2 position of thiadiazole ring and evaluation of their activity against the promastigote and amastigote forms of Leishmania major. Methods: Reaction between the solution of 5-(5-nitro heteroaryl)-2-chloro-1, 3, 4-thiadiazole and piperidin-4-ol in absolute ethanol was performed and the resulting products were evaluated against promastigotes form of L. major with MTT assay and amastigote form of L. major in murine peritoneal macrophages. In addition, the toxicity of these compounds was assessed against mouse peritoneal macrophages with MTT assay. Results: New synthetic compounds 5a-b showed moderate in vitro antileishmanial activity against L. major promastigotes with IC50 values of 68.9 and 27 µM, respectively. These compounds have also demonstrated a good antiamastigote activity in terms of amastigote number per macrophage, the percentage of macrophage infectivity and infectivity index. Conclusion: Novel cyclic compounds 5a-b were synthesized and exhibited less antipromastigote and antiamastigote activity compared to linear analogues. https://jad.tums.ac.ir/index.php/jad/article/view/461 https://jad.tums.ac.ir/index.php/jad/article/download/461/318