Synthesis of new praziquantel analogues: potential candidates for the treatment of schistosomiasis.
An efficient synthesis of antischistosomal drug praziquantel and analogues was achieved and the synthetic route designed was to afford structurally diverse analogues for better structure-activity relationship understanding. Total of nineteen PZQ analogues with structural variations at amide, piperazine and aromatic moieties have been synthesized and fully characterized. Among all the new analogues tested for antischistosomal activity, one dimethoxy tetrahydroisoquinoline analogue and two tetrahydro-β-carboline analogues exhibited moderate activity against adult Schistosoma mansoni. Tetrahydro-β-carboline analogues showed moderate activity whereas the presence of p-trifluoromethylbenzoyl and p-toluenesulphonyl moieties resulted in complete suppression of antischistosomal activity.
Organic Chemistry Division II, Indian Institute of Chemical Technology, Uppal Road Tarnaka, Hyderabad 500607, India.
Partha Sarathi
PS
Sadhu
Singam Naveen
SN
Kumar
Malapaka
M
Chandrasekharam
Livia
L
Pica-Mattoccia
Donato
D
Cioli
Vaidya Jayathirtha
VJ
Rao
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D015394:Molecular Structure; D011223:Praziquantel / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D012550:Schistosoma mansoni / Q000187:drug effects*; D012552:Schistosomiasis / Q000188:drug therapy*; D012556:Schistosomicides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D012556:Schistosomicides; D011223:Praziquantel