Novel 2,3-Dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones: Synthesis and Biological Evaluation

• Published in: Molecules (Basel, Switzerland) Switzerland), 2017-01, Vol.22 (1), p.55-55
• Main Authors: Mphahlele, Malose J, Khoza, Tebogo A, Mabeta, Peaceful
• Format: Article
• Language: English
• Subjects: 1H-pyrrolo[3,2,1-ij]quinazolin-1-ones; Alkynes - chemistry; Antimalarial activity; Antimalarial agents; Antimalarials - chemical synthesis; Antimalarials - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; antiplasmodial activity; Aromatic compounds; Benzaldehyde; Benzaldehydes - chemistry; Benzamides - chemistry; Boric acid; Breast cancer; Cancer; Catalysis; Cell Line, Tumor; Cell Survival - drug effects; Chloroquine; Cross coupling; Cyclization; Cytotoxicity; Endothelial cells; Evaluation; Humans; In vitro methods and tests; Melanoma; Palladium - chemistry; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - growth & development; Pyrroles - chemical synthesis; Pyrroles - pharmacology; Quinazolinones - chemical synthesis; Quinazolinones - pharmacology; Structure-Activity Relationship; Tumor cell lines; Tumors; X-ray
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22010055

Herein we describe the synthesis and evaluation of a series of novel 2,3-dihydro-1 -pyrrolo[3,2,1- ]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 of . The title compounds were prepared via PdCl₂-mediated cyclization of 2-aryl-8-(arylethynyl)-6-bromo-2,3-dihydroquinazolin-4(1 )-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-1 -pyrrolo[3,2,1- ]quinazolin-1-ones - were evaluated for potential in vitro cytotoxicity against the breast (MCF-7), melanoma (B16) and endothelioma (sEnd.2) cell lines. All of the compounds except and were found to be inactive against the three cancer cell lines. Compound substituted 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 pyrroloquinazolinone , 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-1 -pyrrolo[3,2,1- ]quinazolin-1-ones - were found to be inactive against the chloroquine sensitive 3D7 strain of .