title: Anticancer potential of 3-(arylideneamino)-2-phenylquinazoline-4(3H)-one derivatives.
abstract: Different quinazoline derivatives have showed wide spectrum of pharmacological activities. Some 3-(arylideneamino)-phenylquinazoline-4(3H)-ones have been reported to possess antimicrobial activity. The present study has been undertaken to evaluate the anticancer effect of these quinazolinone derivatives. The quinazolinone derivatives were synthesized as reported earlier. Compounds containing NO(2), OH, OCH(3), or OH and OCH(3) as substituent(s) on the arylideneamino group were named as P(3a), P(3b), P(3c), and P(3d) respectively. Out of these, P(3a) and P(3d) showed better cytotoxic activity than P(3b) and P(3c) on a panel of six cancer cell lines of different origin, namely, B16F10, MiaPaCa-2, HCT116, HeLa, MCF7, and HepG2, though the effect was higher in B16F10, HCT116, and MCF7 cells. P(3a) and P(3d) induced death of B16F10 and HCT116 cells was associated with characteristic apoptotic changes like cell shrinkage, nuclear condensation, DNA fragmentation, and annexin V binding. Also, cell cycle arrest at G1 phase, alteration of caspase-3, caspase-9, Bcl-2 and PARP levels, loss of mitochondrial membrane potential, and enhanced level of cytosolic cytochrome c were observed in treated B16F10 cells. Treatment with multiple doses of P(3a) significantly increased the survival rate of B16F10 tumor bearing BALB/c mice by suppressing the volume of tumor while decreasing microvascular density and mitotic index of the tumor cells.
authors.affiliation: Cancer & Cell Biology Division, CSIR, Indian Institute of Chemical Biology, Kolkata, West Bengal, India.
authors.forename: Subhadip
authors.initials: S
authors.lastname: Das
authors.forename: Nabanita
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Dipayan
authors.initials: D
authors.lastname: Bose
authors.forename: Sumit Kr
authors.initials: SK
authors.lastname: Dey
authors.forename: Rudra Narayan
authors.initials: RN
authors.lastname: Munda
authors.forename: Abhishek
authors.initials: A
authors.lastname: Nandy
authors.forename: Sanjoy
authors.initials: S
authors.lastname: Bera
authors.forename: Shyamal Kr
authors.initials: SK
authors.lastname: Biswas
authors.forename: Krishna
authors.initials: K
authors.lastname: Das Saha
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014183:Transplantation, Heterologous
chemical_list: C516488:2-phenylquinazoline; D017304:Annexin A5; D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9