Synthesis, photochemical synthesis and antitumor evaluation of novel derivatives of thieno[3',2':4,5]thieno[2,3-c]quinolones.
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, exhibited 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.
DoganKoruznjak
Jasna
J
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Croatia.
Slade
Neda
N
Zamola
Branimir
B
Pavelić
Kresimir
K
Karminski-Zamola
Grace
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010777:Photochemistry; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D015363:Quinolones; D011944:Receptors, Androgen