Synthesis and antileishmanial activity of fluorinated rhodacyanine analogues: The ‘fluorine-walk’ analysis
Link: https://www.sciencedirect.com/science/article/pii/S0968089619313422
Title: Synthesis and antileishmanial activity of fluorinated rhodacyanine analogues: The ‘fluorine-walk’ analysis
Authors: Thitiya Lasing, Atchara Phumee, Padet Siriyasatien, Kantima Chitchak, Parichatr Vanalabhpatana, Kit-Kay Mak, Chew Hee Ng, Tirayut Vilaivan, Tanatorn Khotavivattana*
Abstract:
In a search for potent antileishmanial drug candidates, eighteen rhodacyanine analogues bearing fluorine or perfluoroalkyl substituents at various positions were synthesized. These compounds were tested for their inhibitory activities against Leishmania martiniquensis and L. orientalis. This ‘fluorine-walk’ analysis revealed that the introduction of fluorine atom at C-5, 6, 5′, or 6′ on the benzothiazole units led to significant enhancement of the activity, correlating with the less negative reduction potentials of the fluorinated analogues confirmed by the electrochemical study. On the other hand, -CF3 and -OCF3 groups were found to have detrimental effects, which agreed with the poor aqueous solubility predicted by the in silico ADMET analysis. In addition, some of the analogues including the difluorinated species showed exceptional potency against the promastigote and axenic amastigote stages (IC50=40–85 nM), with the activities surpassing both amphotericin B and miltefosine.
Cite this:
Lasing, T.; Phumee, A.; Siriyasatien, P.; Chitchak, K.; Vanalabhpatana, P.; Mak, K.-K.; Ng, C. H.; Vilaivan, T.; Khotavivattana, T. Synthesis and antileishmanial activity of fluorinated rhodacyanine analogues: The ‘fluorine-walk’ analysis. Bioorg. Med. Chem. 2020, 28, 115187.
