title: Design, synthesis and pharmacophoric model building of new 3-alkoxymethyl/3-phenyl indole-2-carboxamides with potential antiproliferative activity.
abstract: Novel 3-alkoxymethyl/3-phenyl indole-2-carboxamide derivatives were synthesized and evaluated for their anticancer activity. Most of the tested compounds showed moderate to excellent activity against the tested cell lines (MCF7 and HCT116). 3-Phenyl substitution on indole with p-piperidinyl phenethyl 24a and p-dimethylamino phenethyl 24c exhibited anticancer activity against MCF7 with IC50of 0.13 and 0.14 μm, respectively. Further mechanistic study of the most active compounds through their action on cell cycle showed disturbance in cell cycle progression and cell cycle arrest. For future development of this series of compounds, pharmacophore study was conducted which indicated that the enhancement of the activity could be achieved through the addition of acceptor or donating groups to the already-present indole nucleus.
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
authors.forename: Mostafa H
authors.initials: MH
authors.lastname: Abdelrahman
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Aboraia
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt.|Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Aljouf, Sakaka, Saudi Arabia.
authors.forename: Bahaa G M
authors.identifier: 0000-0002-6834-6548
authors.initials: BGM
authors.lastname: Youssif
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
authors.forename: Bakheet E M
authors.initials: BEM
authors.lastname: Elsadek
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D045325:HCT116 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D061986:MCF-7 Cells; D008958:Models, Molecular; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: C000622439:5-chloro-3-phenyl-N-(4-(piperidin-1-yl)phenethyl)-1H-indole-2-carboxamide; C000622440:5-chloro-N-(4-(dimethylamino)phenethyl)-3-phenyl-1H-indole-2-carboxamide; D000577:Amides; D000970:Antineoplastic Agents; D007211:Indoles; D010880:Piperidines
keywords: anticancer; cell cycle; indole; pharmacophore; synthesis