Novel 5-(nitrothiophene-2-yl)-1,3,4-Thiadiazole Derivatives: Synthesis and Antileishmanial Activity against promastigote stage of Leishmania major

Authors

  • Alireza Foroumadi Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
  • Azadeh Yahya-Meymandi Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • Mahsa Hashemian Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • Marjan Azimzadeh Arani Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
  • Maryam Mirmohammadi Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • Mohammad Hasan Moshafi Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
  • Parham Foroumadi Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • Peiman Norouzi Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • Setareh Moghimi Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
  • Sogol Jafari-Ashtiani Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:

In this study, a series of novel compounds based on 5-(5-nitrothiophene-2-yl)-1,3,4-thiadiazole possessing (het)aryl thio pendant at C-2 position of thiadiazole ring is developed and evaluated as antileishmanial agents using MTT colorimetric assay. 10 New compounds containing aryl and hetero aryl derivatives, started from thiophene-2-carbaldehyde in five steps, were synthesized in good to excellent yields and characterized by 1H-NMR, 13C-NMR and IR spectroscopy. Through the compounds 6a-j, methylimidazole containing derivative 6e was recognized as the most active compound against L. major promastigotes exhibiting IC50 values of 11.2µg/ml and 7.1µg/ml after 24 and 48 hours, respectively. This compound is >4 fold more effective than Glucantime as a standard drug (IC50 = 50 µg/ml after 24 h and 25 µg/ml after 48 h).

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Journal title

volume 18  issue 4

pages  1816- 1822

publication date 2019-12-01

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