title: Synthesis of novel morpholine conjugated benzophenone analogues and evaluation of antagonistic role against neoplastic development.
abstract: A series of novel 4-benzyl-morpholine-2-carboxylic acid N'-[2-(4-benzoyl-phenoxy)-acetyl]-hydrazide derivatives 8a-j has been synthesized from (4-hydroxy-aryl)-aryl methanones through a multi-step reaction sequence and then evaluated for anti-proliferative activity in vitro against various types of neoplastic cells of mouse and human such as DLA, EAC, MCF-7 and A549 cells. From the cytotoxic studies and structural activity relationship of compounds 8a-j, it is clear that methyl group on the B ring of benzophenone is essential for antiproliferative activity and bromo at ortho position (compound 8b) and methyl at para position (compound 8f) on A ring of benzophenone are significant for extensive anti-mitogenic activity. Investigation on clonogenesis and Fluorescence-activated cell sorting suggests that compounds 8b and 8f have the potency to exhibit the prolonged activity with cell cycle arrest on G2/M phase against cancer progression. Further, the compounds 8b and 8f inhibit murine ascites lymphoma through caspase activated DNase mediated apoptosis.
authors.affiliation: Department of Chemistry, Yuvaraja's College, University of Mysore, Mysore 570005, Karnataka, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Ghorbani
authors.affiliation: Molecular Onco-medicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (A), Kuvempu University, Shimoga 577203, Karnataka, India.
authors.forename: Prabhu
authors.initials: P
authors.lastname: Thirusangu
authors.affiliation: Department of Chemistry, Yuvaraja's College, University of Mysore, Mysore 570005, Karnataka, India.
authors.forename: H D
authors.initials: HD
authors.lastname: Gurupadaswamy
authors.affiliation: Molecular Onco-medicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (A), Kuvempu University, Shimoga 577203, Karnataka, India.
authors.forename: V
authors.initials: V
authors.lastname: Vigneshwaran
authors.affiliation: Department of Chemistry, Yuvaraja's College, University of Mysore, Mysore 570005, Karnataka, India.
authors.forename: Yasser H E
authors.initials: YH
authors.lastname: Mohammed
authors.affiliation: Molecular Onco-medicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (A), Kuvempu University, Shimoga 577203, Karnataka, India.
authors.forename: B T
authors.initials: BT
authors.lastname: Prabhakar
authors.affiliation: Department of Chemistry, Yuvaraja's College, University of Mysore, Mysore 570005, Karnataka, India. Electronic address: shaukathara@yahoo.co.in.
authors.forename: Shaukath Ara
authors.initials: SA
authors.lastname: Khanum
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001577:Benzophenones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D051379:Mice; D009025:Morpholines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001577:Benzophenones; D009025:Morpholines
keywords: Benzophenone; CAD; DLA; MCF-7; Morpholine