title: Quinazolinones-Phenylquinoxaline hybrids with unsaturation/saturation linkers as novel anti-proliferative agents.
abstract: A new series of novel quinazolinones with allylphenyl quinoxaline hybrids 9a-n were efficiently synthesized in good yields by the reaction of 3-allyl-2-methylquinazolin-4(3H)-one (5a-n) with bromophenyl)quinoxaline (8) utilizing Pd catalyzed Heck-cross coupling and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 9a, 9e, 9g and 9h exhibited promising anti-proliferative activity with GI50 values ranging from 0.06 to 0.2μM against four cell lines, while compounds 9e and 9k showed significant activity against HeLa and MIAPACA cell lines and compounds 9b, 9d, 9h and 9j showed selective potency against IMR32 and MDA-MB-231 cell lines. This is the first report on the synthesis and in vitro anti-proliferative evaluation of E-2-(4-substituted)-3-(3-(4-(quinoxalin-2-yl)phenyl)allyl)quinazolin-4(3H)-ones (9a-n). Docking results indicate a sign of good correlation between experimental activity and calculated binding affinity (dock score), suggesting that these compounds could act as promising DNA intercalates.
authors.affiliation: Organic Chemistry Division II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: Jyothsna Devi
authors.initials: JD
authors.lastname: Palem
authors.affiliation: Organic Chemistry Division II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: Gopi Reddy
authors.initials: GR
authors.lastname: Alugubelli
authors.affiliation: Organic Chemistry Division II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: Rajashaker
authors.initials: R
authors.lastname: Bantu
authors.affiliation: Organic Chemistry Division II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India. Electronic address: lnagarapuiict@yahoo.com.
authors.forename: Lingaiah
authors.initials: L
authors.lastname: Nagarapu
authors.affiliation: Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: Sowjanya
authors.initials: S
authors.lastname: Polepalli
authors.affiliation: Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: S Nishanth
authors.initials: SN
authors.lastname: Jain
authors.affiliation: Molecular Modeling and Medicinal Chemistry Group, Department of Chemistry, Osmania University, Tarnaka, Hyderabad 500007, India.
authors.forename: Raju
authors.initials: R
authors.lastname: Bathini
authors.affiliation: Molecular Modeling and Medicinal Chemistry Group, Department of Chemistry, Osmania University, Tarnaka, Hyderabad 500007, India.
authors.forename: Vijjulatha
authors.initials: V
authors.lastname: Manga
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D062105:Molecular Docking Simulation; D017239:Paclitaxel / Q000494:pharmacology; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007364:Intercalating Agents; D052999:Quinazolinones; D011810:Quinoxalines; D004317:Doxorubicin; D004247:DNA; D017239:Paclitaxel
keywords: Allylphenyl quinoxaline; Anti-proliferative activity; Cancer cell lines; DNA intercalates; Heck-cross coupling; Quinazolinones