title: Synthesis of 2,3,6,7-tetramethoxyphenanthren-9-amine: An efficient precursor to access new 4-aza-2,3-dihydropyridophenanthrenes as apoptosis inducing agents.
abstract: A new route for the synthesis of novel 2,3,6,7-tetramethoxy phenanthrene amine precursor has been successfully accomplished. Subsequently, this amine precursor has been directly utilized for the synthesis of a new series of 4-aza-2,3-dihydropyridophenanthrene derivatives via a three component reaction with tetronic acid and substituted aldehydes. These compounds were evaluated for their cytotoxic potential against human lung (A549), prostate (PC-3 and DU145), breast (MDA-MB-231 and 4T1), gastric (HGC-27), colon (Caco-2) and cervical (HeLa) cancer cell lines. Compound 10l showed significant anticancer profile against DU145 cell line with an IC50value of 2.6 ± 0.34 μM. Disruption of F-actin cytoskeleton structure and cell migration inhibition in DU145 cells clearly indicate that the tumor progression and metastasis are affected by this compound (10l). Cell cycle analysis revealed that it arrests the cells in G2/M phase. Acridine orange/ethidium bromide (AO/EB) staining, Hoechst staining and annexin-V binding assays showed that cell proliferation is inhibited through induction of apoptosis. Moreover, its treatment leads to collapse of the mitochondrial membrane potential (DΨm).
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Niggula Praveen
authors.initials: NP
authors.lastname: Kumar
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne 3001, Australia.
authors.forename: T Srinivasa
authors.initials: TS
authors.lastname: Reddy
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Nekkanti
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.in.
authors.forename: Nagula
authors.initials: N
authors.lastname: Shankaraiah
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Guntuku
authors.initials: G
authors.lastname: Lalita
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: S
authors.initials: S
authors.lastname: Sujanakumari
authors.affiliation: Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne 3001, Australia.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Bhargava
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: V G M
authors.initials: VGM
authors.lastname: Naidu
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: ahmedkamal@iict.res.in.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010616:Phenanthrenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010616:Phenanthrenes; C031181:phenanthrene
keywords: 2,3,6,7-Tetramethoxyphenanthren-9-amine; 4-Aza-2,3-dihydropyridophenanthrenes; Apoptosis; Cytotoxicity; Multi-component reaction; Perkin condensation