Synthesis and Evaluation of Novel 2,2-Dimethylthiochromanones as Anti-Leishmanial Agents
Seán Coll,
Mohammad Alhazmi,
Patrícia de Aguiar Amaral,
Sandra Bourgeade-Delmas,
Anne-Cécile Le Lamer,
James W. Barlow
Affiliations
Seán Coll
Department of Chemistry, RCSI University of Medicine and Health Sciences, 123 St. Stephen’s Green, Dublin 2, Ireland
Mohammad Alhazmi
Department of Chemistry, RCSI University of Medicine and Health Sciences, 123 St. Stephen’s Green, Dublin 2, Ireland
Patrícia de Aguiar Amaral
Laboratory of Medicinal Plants (LaPlaM/PPGCA), Universidade do Extremo Sul Catarinense (UNESC), Avenida Universitária 1105, Bairro Universitário, Criciúma 88806-000, SC, Brazil
Sandra Bourgeade-Delmas
UMR 152 IRD-UPS PHARMADEV, Faculté des Sciences Pharmaceutiques, Université Toulouse III-Paul Sabatier, 35 Chemin des Maraîchers, 31062 Toulouse CEDEX 09, France
Anne-Cécile Le Lamer
UMR 152 IRD-UPS PHARMADEV, Faculté des Sciences Pharmaceutiques, Université Toulouse III-Paul Sabatier, 35 Chemin des Maraîchers, 31062 Toulouse CEDEX 09, France
James W. Barlow
Department of Chemistry, RCSI University of Medicine and Health Sciences, 123 St. Stephen’s Green, Dublin 2, Ireland
Within this work, we describe the design and synthesis of a range of novel thiochromanones based on natural products reported to possess anti-leishmanial action, and their synthetic derivatives. All compounds were elaborated via the key intermediate 2,2,6-trimethoxythiochromanone, which was modified at the benzylic position to afford various ester, amine and amide analogues, substituted by chains of varying lipophilicity. Upon testing in Leishmania, IC50 values revealed the most potent compounds to be phenylalkenyl and haloalkyl amides 11a and 11e, with IC50 values of 10.5 and 7.2 μM, respectively.