Naslov
Synthesis, photochemical synthesis and antitumor evaluation of novel derivatives of thieno(3', 2':4, 5)thieno(2, 3-c)quinolones

Autori
Dogan Koružnjak, Jasna ; Slade, Neda ; Zamola, Branimir ; Pavelić, Kresimir ; Karminski-Zamola, Grace

Izvornik
Chemical and pharmaceutical bulletin (0009-2363) 50 (2002), 5; 656-660

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

Ključne riječi
quinolone ; thiophene ; antitumor activity ; heck reaction ; photocyclization ; alkylation

Sažetak
The novel derivatives of thieno(3'2':4.5)thieno(2, 3-c)quinolones 6a, 6b, 7, 10a and 10b were synthesized in multistep synthesis starting from thiophene-3-carboxaldehyde and malonic acid reacting in aldol condensation or from 3-bromothiophenes or methyl 4-bromothiophene-2-carboxylate reacting in Heck reaction. They resulted in corresponding substituted thienylacrylic acids 3a-c, which were cyclized into thieno(2, 3-c)thiophene-2-carbonyl chlorides 4a-c and converted into thieno(2, 3-c)thiophene-2-carboxamides 5a-d. Prepared carboxamides were photochemically dehydrohalogenated into corresponding substituted thieno(3', 2':4, 5)thieno(2, 3-c)quinolones 6a-d. Compound 7 was prepared from 6d by alkylation with N-(3-(dimethylamino)propyl)chloride hydrochloride in the presence of NaH. Compounds 10a and 10b were prepared from 6c in the multistep synthesis over acid 8 and acid chloride 9. Compounds 6a, 6b, 7, 10a and 10b were found to exert cytostatic activities against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), colon carcinoma (CaCo-2), melanoma (HBL), and human fibroblast cell lines (WI-38). The compound 6b, which bears the 3-dimethylaminopropyl substituent on quinolone nitrogen and methoxycarbonyl substituent on position 9 exhibiedt marked antitumor activity. On the contrary, compound 7, which also bears the 3-dimethylaminopropyl substituent on the quinolone nitrogen but anilido substituent on position 9, exhibited less antitumor activity than the others.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti

POVEZANOST RADA