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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996
EISSN: 1596-9827
Vol. 14, No. 11, 2015, pp. 1975-1981
Bioline Code: pr15258
Full paper language: English
Document type: Research Article
Document available free of charge

Tropical Journal of Pharmaceutical Research, Vol. 14, No. 11, 2015, pp. 1975-1981

 en In vitro Anti-Leishmania Activity and Safety of Newly Synthesized Thiazolo Pyrimidine Derivatives Augmented with Interleukine-12 (IL-12) in BALB/c Mice Experimentally- Infected with Cutaneous Leishmaniasis
Bahashwan, Saleh A.; Ramadan, Mohamed A.; Aboonq, Moutasem S. & Fayed, Ahmed A.


Purpose: To synthesize a series of novel thiazolo pyrimidine derivatives and evaluate them in vitro and in vivo for their safety and anti-leishmanial activity using BALB/c mice.
Methods: Substituted pyrazolopyrimidine and pyrazolopyrazole were synthesized by reacting amino group of 2-amino-4-cyano-pyrazol]naphthalino[1,2-d]thiazole with a variety of formamide or hydrazine hydrate. The synthesized compounds were characterized by nuclear magnetic resonance spectroscopy (1H-NMR) and mass spectroscopy (MS). The purity of the compounds was determined by elemental analysis. Safety and anti-leishmanial activity of the compounds were determined in vitro by i) viability assessment of leishmania-infected macrophages, relative abundance of IL-12p40 mRNA gene expression and levels of IL10 /IL-12 determination in supernatants of cultured macrophages treated with 2.5 and 10 μM of the compounds, using microscope cell counting, reverse transcriptase polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. ii) cytotoxicity of the compounds evaluated by determination the safety index as IC50 of the compound in macrophages/IC50 of the compound in amastigotes. iii) bioassay at 16 weeks post-infection of mice treated with the reference drug, the tested compound alone and both the compound with IL-12. Disease progression and footpad thickness were evaluated regularly during treatment.
Results: Compound 4 emerged as the most active anti-protozoal compound of the series against Leishmania viability (activity 60 %) compared with the reference drug (activity 65 %). When it was combined with IL-12, the activity reached 90 %.
Conclusion: Compound 4 can serve as a lead molecule for further development to a clinically useful novel class of agents.

Thiazolopyrimidine; Synthesis; Leishmaniasis; Mice; Immunotherapy

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