Structure-Bioactivity Relationships of Lapatinib Derived Analogs against Schistosoma mansoni

Melissa J Buskes; Monica Clements; Kelly A Bachovchin; Hitesh B Jalani; Allison Leonard; Seema Bag; Dana M Klug; Baljinder Singh; Robert F Campbell; Richard J Sciotti; Nelly El-Sakkary; Conor R Caffrey; Michael P Pollastri; Lori Ferrins

doi:10.1021/acsmedchemlett.9b00455

Structure-Bioactivity Relationships of Lapatinib Derived Analogs against Schistosoma mansoni

ACS Med Chem Lett. 2020 Jan 10;11(3):258-265. doi: 10.1021/acsmedchemlett.9b00455. eCollection 2020 Mar 12.

Affiliations

¹ Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
² Experimental Therapeutics, Walter Reed Army Institute of Research, 2460 Linden Lane, Silver Spring, Maryland 20910, United States.
³ Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, United States.

Abstract

We recently reported a series of compounds for a solubility-driven optimization campaign of antitrypanosomal compounds. Extending a parasite-hopping approach to the series, a subset of compounds from this library has been cross-screened for activity against the metazoan flatworm parasite, Schistosoma mansoni. This study reports the identification and preliminary development of several potently bioactive compounds against adult schistosomes, one or more of which represent promising leads for further assessment and optimization.