Naslov
Novel 2-Thienyl- and 2-Benzothienyl-Substituted 6-(2-Imidazolinyl)Benzothiazoles: Synthesis ; in vitro Evaluation of Antitumor Effects and Assessment of Mitochondrial Toxicity

Autori
Racané, Livio ; Sedić, Mirela ; Ilić, Nataša ; Aleksić, Maja ; Kraljević Pavelić, Sandra ; Karminski-Zamola, Grace

Izvornik
Anti-Cancer Agents in Medicinal Chemistry (1871-5206) 17 (2017), 1; 57-66

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

Ključne riječi
thieny- ; benzothienyl- ; imidazolinyl- substituted benzothiazoles ; acid ceramidase inhibitor ; sphingosine kinase 1 inhibitor

Sažetak
A series of novel cationic 2-thiophene and 2-benzothiophene substituted 6-(2-imidazolinyl)benzothiazole derivatives were prepared and tested for their antiproliferative activity against several human cancer cell lines. An efficient synthesis approach used for the preparation of water soluble mesylate salts 3a-3j of title compounds was achieved by the condensation reaction of 2-amino-5-(2-imidazolinium)benzenethiolate with aldehydes or carbonyl chloride derivatives followed by two simple acid-base reaction steps for their conversion into targeted mesylates. In general, all compounds showed pronounced anticancer activities in vitro. Compound 3f showed strong and selective cytostatic activity in cervical carcinoma cells (HeLa) with moderate toxicity on normal fibroblasts. Similar to all other tested compounds, 3f cannot be considered mitochondrial toxicant. One of the major mechanisms accounting for observed cytostatic effects of 3f was induction of apoptosis, probably due to specific inhibition of acid ceramidase activity. Compound 3h negatively regulated activity of sphingosine kinase 1 in HeLa cells. Thus, design of novel inhibitors targeting enzymes that regulate sphingolipid biosynthesis and turnover could change the landscape for the development of new anticancer drugs.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Temeljne medicinske znanosti

Napomena
Rad je finaciran od HRZZ-IP-11-2013-5596. Prvi autor je Livio Racane, koji radi na navedenom projektu.

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