title: Structure based drug design, synthesis and evaluation of 4-(benzyloxy)-1-phenylbut-2-yn-1-ol derivatives as 5-lipoxygenase inhibitors.
abstract: A group of 4-(benzyloxy)-1-phenylbut-2-yn-1-ol derivatives were designed using Site point connection method, synthesized and evaluated for their 5-Lipoxygenase (5-LOX) inhibitory activity. Hydrophobic site points in 5-LOX were considered for the study and substitutions were planned such that 4k will have strong hydrophobic group in the corresponding site point. Biological results supported the in silico prediction with compound 4k exhibiting good inhibition with IC(50) value of 8 μM against 5-LOX. The compounds 4j and 4k showed potent cytotoxic effects against various cancer cell lines (COLO-205, MDA-MB-231 and HepG2) but with no effect on normal cell line (HaCaT). The overall trend showed 4k as the most potent compound. Further studies demonstrated the protective effect of 4k in mouse Acute Lung Injury (ALI) model induced by lipopolysaccharide (LPS).
authors: School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India.
authors: Nimmanapalli P
authors: NP
authors: Reddy
authors: T
authors: T
authors: Chandramohan Reddy
authors: Polamarasetty
authors: P
authors: Aparoy
authors: Chandrani
authors: C
authors: Achari
authors: P Ramu
authors: PR
authors: Sridhar
authors: Pallu
authors: P
authors: Reddanna
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry / Q000378:metabolism*; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000440:Butanols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: C572362:4-(benzyloxy)-1-phenylbut-2-yn-1-ol; D001593:Benzyl Compounds; D000440:Butanols; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase