title: Novel 2,3-Dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones: Synthesis and Biological Evaluation.
abstract: Herein we describe the synthesis and evaluation of a series of novel 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones for in vitro cytotoxicity against three human cancer cell lines as well as for potential antimalarial activity against the chloroquine-sensitive strain 3D7 ofPlasmodium falciparum. The title compounds were prepared via PdCl₂-mediatedendo-digcyclization of 2-aryl-8-(arylethynyl)-6-bromo-2,3-dihydroquinazolin-4(1H)-ones. The latter were prepared, in turn, via initial Sonogashira cross-coupling of 2-amino-5-bromo-3-iodobenzamide with aryl acetylenes followed by boric acid-mediated cyclocondensation of the intermediate 2-amino-3-(arylethynyl)-5-bromobenzamides with benzaldehyde derivatives. The 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones4a-kwere evaluated for potential in vitro cytotoxicity against the breast (MCF-7), melanoma (B16) and endothelioma (sEnd.2) cell lines. All of the compounds except4hand4iwere found to be inactive against the three cancer cell lines. Compound4hsubstituted with a 4-methoxyphenyl and 4-fluorophenyl groups at the 3- and 5-positions was found to exhibit significant cytotoxicity against the three cancer cell lines. The presence of phenyl and 3-chlorophenyl groups at the 3- and 5-posiitons of the pyrroloquinazolinone4i, on the other hand, resulted in significant cytotoxicity against vascular tumour endothelial cells (sEnd.2), but reduced activity against the melanoma (B16) and breast cancer (MCF-7) cells except at higher concentrations. The 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones4a-lwere found to be inactive against the chloroquine sensitive 3D7 strain ofPlasmodium falciparum.
authors.affiliation: Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa. mphahmj@unisa.ac.za.
authors.forename: Malose J
authors.initials: MJ
authors.lastname: Mphahlele
authors.affiliation: Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa. khozata@unisa.ac.za.
authors.forename: Tebogo A
authors.initials: TA
authors.lastname: Khoza
authors.affiliation: Department of Anatomy and Physiology, University of Pretoria, P/Bag X04, Pretoria 0110, South Africa. Peace.Mabeta@up.ac.za.
authors.forename: Peaceful
authors.initials: P
authors.lastname: Mabeta
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001547:Benzaldehydes / Q000737:chemistry; D001549:Benzamides / Q000737:chemistry; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003500:Cyclization; D006801:Humans; D010165:Palladium / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D000962:Antimalarials; D000970:Antineoplastic Agents; D001547:Benzaldehydes; D001549:Benzamides; D011758:Pyrroles; D052999:Quinazolinones; D010165:Palladium; C008756:palladium chloride
keywords: 1H-pyrrolo[3,2,1-ij]quinazolin-1-ones; Plasmodium falciparum; X-ray; antiplasmodial activity; cytotoxicity