Novel Derivatives of Benzo[b]thieno[2,3-c]quinolones:  Synthesis, Photochemical Synthesis, and Antitumor Evaluation

Dogan Koružnjak, Jasna; Grdiša, Mira; Slade, Neda; Zamola, Branimir; Pavelić, Krešimir; Karminski-Zamola, Grace

doi:10.1021/jm0210966

Pregled bibliografske jedinice broj: 119053

Novel Derivatives of Benzo[b]thieno[2,3-c]quinolones: Synthesis, Photochemical Synthesis, and Antitumor Evaluation

Dogan Koružnjak, Jasna; Grdiša, Mira; Slade, Neda; Zamola, Branimir; Pavelić, Krešimir; Karminski-Zamola, Grace

Novel Derivatives of Benzo[b]thieno[2,3-c]quinolones: Synthesis, Photochemical Synthesis, and Antitumor Evaluation // Journal of medicinal chemistry, 46 (2003), 21; 4516-4524 doi:10.1021/jm0210966 (međunarodna recenzija, članak, znanstveni)

CROSBI ID: 119053 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Novel Derivatives of Benzo[b]thieno[2,3-c]quinolones: Synthesis, Photochemical Synthesis, and Antitumor Evaluation

Autori
Dogan Koružnjak, Jasna ; Grdiša, Mira ; Slade, Neda ; Zamola, Branimir ; Pavelić, Krešimir ; Karminski-Zamola, Grace

Izvornik
Journal of medicinal chemistry (0022-2623) 46 (2003), 21; 4516-4524

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
derivatives of benzo((b)thieno(2, 3-c)quinolones ; antitumor effect ; synthesis

Sažetak
Novel derivatives of benzo(b)thieno(2, 3-c)quinolones 3a-j were synthesized in a multistep synthesis starting from substituted benzo(b)thiophene-2-carbonyl chlorides, to their corresponding benzo(b)thiophene-2-carboxamides, which were photochemically dehydrohalogenated to their corresponding substituted benzo(b)thieno(2, 3-c)quinolones. Compound 4 was prepared from 3i by alkylation with 3-dimethylaminopropyl chloride in the presence of NaH. Compounds 7a, b were prepared from 3g in the multistep synthesis from compounds 5 and 6. Compounds 3b, 3c-f, 3h, 7a, and 7b were found to exert cytostatic activity against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), colon carcinoma (CaCo-2), melanoma (HBL), human fibroblast cell lines (WI-38). The compounds that bear a 3-dimethylaminopropyl substituent on the quinolone nitrogen (3b, 3c-f, 3h) showed higher antitumor activity than compounds bearing the same substituent on the amidic nitrogen (7a and 7b). The compound 3h, which has a 3-dimethylaminopropyl substituent on the quinolone nitrogen and a methoxycarbonyl substituent at position 9, had marked antitumor activity. Because of strong cytotoxic effect of compound 4 on melanoma cells (HBL, ME 67.3 and ME 67.1) a potential mechanism of action was examined. Analysis of DNA and Annexin-V-FLUOS staining indicated that compound 4 causes cell death by apoptosis.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti

POVEZANOST RADA

Projekti:
0125005
0098093
0098092

Ustanove:
Prehrambeno-biotehnološki fakultet, Zagreb,
Institut "Ruđer Bošković", Zagreb,
Fakultet kemijskog inženjerstva i tehnologije, Zagreb

Profili:

Branimir Zamola (autor)