Synthesis and Preliminary Cytotoxicity Studies of 1-[1-(4,5-Dihydrooxazol- 2-yl)-1H-indazol-3-yl]-3-phenylurea and 3-phenylthiourea Derivatives.

Abstract

BACKGROUND:

N-substituted 3-amino-1H-indazoles represent an interesting class of biologically active compounds. Among them, derivatives containing phenylurea moiety are of particular interest. Such compounds have been found to possess inhibitory activity against cancer cell growth. Additionally, various oxazoline-containing compounds have also been designed as potential anticancer agents.

OBJECTIVE:

The aim of this work was to obtain a new class of N-substituted 3-amino-1H-indazole derivatives with cytotoxic activity towards cancer cells.

METHOD:

Two series of 1-[1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl]-3-phenylurea and 3- phenylthiourea derivatives 7-17 and 18-22, respectively, were prepared and screened for their potential in vitro cytotoxic activities against lung carcinoma LCLC-103H cell line using a crystal violet microtiter plate assay.

RESULTS:

All the urea derivatives, except the compound 8, were inactive at a concentration of 20 μM attainable in cancer cells, while the thiourea derivatives showed a pronounced cancer cell growth inhibitory effects. The most potent 1-[1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl]-3-ptolylthiourea (19) exhibited cytotoxicity on the lung cancer LCLC-103H and cervical cancer SISO cell lines at a concentration of 10 µM. Moreover, compound 19 displayed cytostatic activity against pancreas cancer DAN-G cell line.

CONCLUSION:

The 1-[1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl]-3-phenylthiourea derivatives described herein may serve as a useful scaffold for the search for novel anticancer agents.

• Authors: Anita Kornicka, Franciszek Saczewski, Patrick J Bednarski, Martyna Korcz, Piotr Szumlas, Ewa Romejko, Aneta Sakowicz, Lukasz Sitek, Monika Wojciechowska
• Journal: Medicinal chemistry (Shariqah (United Arab Emirates)) (Med Chem) Vol. 13 Issue 7 Pg. 616-624 ( 2017) ISSN: 1875-6638 [Electronic] Netherlands
• PMID: 28266278 (Publication Type: Journal Article)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• 1-(1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl)-3-ptolylthiourea
• Antineoplastic Agents
• Indazoles
• Phenylurea Compounds
• Thiourea

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Humans
• Indazoles (chemical synthesis, pharmacology)
• Phenylurea Compounds (chemical synthesis, pharmacology)
• Thiourea (analogs & derivatives, chemical synthesis, pharmacology)