title: Structure-based approach to falcipain-2 inhibitors: synthesis and biological evaluation of 1,6,7-trisubstituted dihydroisoquinolines and isoquinolines.
abstract: 1,4,7-Trisubstituted isoquinolines were designed, synthesized and evaluated for their inhibition against Plasmodium falciparum cysteine protease falcipain-2. The 1-benzyloxyphenyl-dihydroisoquinoline and -isoquinoline derivatives were found to exhibit better activity against falcipain-2 than their corresponding 1-hydroxyphenyl or 1-methoxyphenyl analogues. The docking scores correlate with the IC(50) values of compounds and give a high coefficient correlation of 0.94.
authors.affiliation: Medicinal Chemistry Division, Central Drug Research Institute, 226001 Lucknow, India. batra_san@yahoo.co.uk
authors.forename: Sanjay
authors.initials: S
authors.lastname: Batra
authors.forename: Yogesh A
authors.initials: YA
authors.lastname: Sabnis
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Avery
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006865:Hydrogenation; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D016415:Sequence Alignment; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D015853:Cysteine Proteinase Inhibitors; D007546:Isoquinolines; D003546:Cysteine Endopeptidases; C416224:falcipain 2