Synthesis and Anticancer Activity of Some 1H-inden-1-one Substituted (Heteroaryl)Acetamide Derivatives

Author(s): Ahmet Cagri Karaburun, Nalan Gundogdu-Karaburun*, Leyla Yurttas, Ismail Kayagil, Seref Demirayak.

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: The synthesis of 2-[3/4-((6-substituted-1-oxo-2,3-dihydro-1H-inden-2- ylidene)methyl)phenoxy]-N-(heteroaryl)acetamide derivatives and the investigation of their anticancer activity were studied.

Methods: 2-(3/4-Hydroxybenzylidene)-6-substituted-2,3-dihydro-1H-inden-1-ones were reacted with suitable 2-chloroacetamides to give 2-[3/4-((6-substituted-1-oxo-2,3-dihydro-1H-inden-2-ylidene) methyl)phenoxy]-N-(heteroaryl)acetamide derivatives.

Results: The structure elucidation of the newly synthesised 16 compounds was performed by IR, 1H-NMR, mass spectroscopic data and elemental analyses. The anticancer screening was carried out in National Cancer Institute (NCI), USA.

Conclusion: Compound 3e (2-(3-((6-chloro-1-oxo-2,3-dihydro-1H-inden-2-ylidene)methyl)phenoxy)- N-(thiazol-2-yl)acetamide), exhibited highest growth inhibition against the leukaemia (61.47%), non-small cell lung cancer (79.31%) and breast cancer (62.82%) cell lines.

Keywords: Anticancer activity, aurone analogue, benzothiazoleacetamide, 2, 3-dihydro-1H-inden-1-one, thiazoleacetamide, leukaemia.

Modranka, J.; Albrecht, A.; Jakubowski, R.; Krawczyk, H.; Rózalski, M.; Krajewska, U.; Janecka, A.; Wyrebska, A.; Rózalska, B.; Janecki, T. Synthesis and biological evaluation of a-methylidene-d-lactones with 3,4-dihydrocoumarin skeleton. Bioorg. Med. Chem. Lett., 2012, 20, 5017-5026.
Keri, R.S.; Budagumpi, S.; Pai, R.K.; Balakrishna, R.G. Chromones as a privileged scaffold in drug discovery: A review. Eur. J. Med. Chem., 2014, 78, 340-374.
Emami, S.; Ghanbarimasir, Z. Recent advances of chroman-4-one derivatives: Synthetic approaches and bioactivities. Eur. J. Med. Chem., 2015, 26, 539-563.
Seifert, T.; Malo, M.; Kokkola, T.; Engen, K.; Fridén-Saxin, M.; Wallén, E.A.A.; Kakkonen, L.M.; Jarho, E.M.; Luthman, K. Chroman-4-one- and chromone-based sirtuin 2 inhibitors with antiproliferative properties in cancer cells. J. Med. Chem., 2014, 57, 9870-9888.
Alizadeh, B.H.; Saeedi, M.; Dehghan, G.; Foroumadi, A.; Shafiee, A. Synthesis of some novel pyrano [2,3-f]chromenone derivatives. J. Iran Chem. Soc, 2015, 12, 605-612.
Lawrence, N.J.; Rennison, D.; McGown, A.T.; Hadfield, J.A. The total synthesis of an aurone isolated from Uvaria hamiltonii: Aurones and flavones as Anticancer Agents. Bioorg. Med. Chem. Lett., 2003, 13, 3759-3763.
Haudecoeur, R.; Boumendjel, A. Recent advances in the medicinal chemistry of aurones. Curr. Med. Chem., 2012, 19, 2861-2875.
Kandioller, W.; Kubanik, M.; Bytzek, A.K.; Jakupec, M.A.; Roller, A.; Keppler, B.K.; Hartinger, C.G. The rearrangement of tosylated flavones to 10-(alkylamino)aurones with primary amines. Tetrahedron, 2015, 71, 8953-8959.
Zwergel, C.; Valente, S.; Salvato, A.; Xu, Z.; Talhi, Q.; Mai, A.; Silva, A.; Altuccice, L.; Kirsch, G. Novel benzofuran-chromone and -coumarin derivatives: Synthesis and biological activity in K562 human leukemia cells. MedChemComm, 2013, 4, 1571-1579.
Cheng, H.; Zhang, L.; Liu, Y.; Chen, S.; Cheng, H.; Lu, X.; Zheng, Z.; Zhou, G.C. Design, synthesis and discovery of 5-hydroxyaurone derivatives as growth inhibitors against HUVEC and some cancer cell lines. Eur. J. Med. Chem., 2010, 45, 5950-5957.
Sim, H.; Lee, C.; Rachel, P.L.; Go, M.L. Dimethoxyaurones: Potent inhibitors of ABCG2 (breast cancer resistance protein). Eur. J. Pharm. Sci., 2008, 35, 293-306.
Gundogdu-Karaburun, N.; Karaburun, A.C.; Demirayak, S.; Kayagil, I.; Yurttas, L. Synthesis and anticancer activity of some 2-[3/4-(2-substituted phenyl-2-oxoethoxy)benzylidene]-6-substituted-2,3-dihydro-1H-inden-1-one derivatives. Lett. Drug Des. Discov., 2014, 11, 578-585.
Demirayak, S.; Yurttas, L.; Gundogdu-Karaburun, N.; Karaburun, A.C.; Kayagil, I. Synthesis and anticancer activity evaluation of new aurone derivatives. J. Enzyme Inhib. Med. Chem., 2014, 30, 816-825.
Demirayak, S.; Yurttas, L.; Karaburun, A.C.; Gundogdu-Karaburun, N.; Kayagil, I. Synthesis and antiproliferative activity of 2-arylidene 6-(2-aryl-2-oxoethoxy)benzofuran-3-one derivatives. Lett. Drug Des. Discov., 2016, 13, 563-569.
Demirayak, S.; Yurttas, L.; Gundogdu-Karaburun, N.; Karaburun, A.C.; Kayagil, I. New chroman-4-one/thiochroman-4-one derivatives as potential anticancer agents. Saudi Pharm. J., 2017, 25, 1063-1072.
El-Damasy, A.K.; Lee, J.H.; Seo, S.H.; Cho, N.C.; Pae, A.N.; Keum, G. Design and synthesis of new potent anticancer benzothiazole amides and ureas featuring pyridylamide moiety and possessing dual B-Raf V600E and C-Raf kinase inhibitory activities. Eur. J. Med. Chem., 2016, 115, 201-216.
Zhao, H.; Cui, G.; Jin, J.; Chen, X. Xu. B. Synthesis and Pin1 inhibitory activity of thiazole derivatives. Bioorg. Med. Chem., 2016, 24, 5911-5920.
Lad, N.P.; Manohar, Y.; Mascarenhas, M.; Pandit, Y.B.; Kulkarni, M.R.; Sharma, R.; Salkar, K.; Suthar, A.; Pandit, S.S. Methylsulfonyl benzothiazoles (MSBT) derivatives: Search for new potential antimicrobial and anticancer agents. Bioorg. Med. Chem. Lett., 2017, 27, 1319-1324.
Das, J.; Lin, J.; Moquin, R.V.; Shen, Z.; Spergel, S.H.; Wityak, J.; Doweyko, A.M.; DeFex, H.F.; Fang, Q.; Pang, S.; Pitt, S.; Shen, D.R.; Schieven, G.L.; Barrish, J.C. Molecular design, synthesis, and structure-activity relationships leading to the potent and selective P56lck inhibitor BMS-243117. Bioorg. Med. Chem. Lett., 2003, 13, 2145-2149.
Yoshida, M.; Hayakawa, I.; Hayashi, N.; Agatsuma, T.; Oda, Y.; Tanzawa, F.; Iwasaki, S.; Koyama, K.; Furukawa, H.; Kurakata, S.; Sugano, Y. Synthesis and biological evaluation of benzothiazole derivatives as potent antitumor agents. Bioorg. Med. Chem. Lett., 2005, 15, 3328-3332.
Pradidphol, N.; Kongkathip, N.; Sittikul, P.; Boonyalai, N.; Kongkathip, B. First synthesis and anticancer activity of novel naphthoquinone amides. Eur. J. Med. Chem., 2012, 49, 253-270.
Yang, X.H.; Xiang, L.; Li, X.; Zhaoa, T.T.; Zhang, H.; Zhou, W.P.; Wang, X.M.; Gong, H.B.; Zhu, H.L. Synthesis, biological evaluation, and molecular docking studies of 1,3,4-thiadiazol-2-amide derivatives as novel anticancer agents. Bioorg. Med. Chem., 2012, 20, 2789-2795.
Mathew, B.; Hobrath, J.V.; Connelly, M.C.; Kiplin Guy, R.; Reynolds, R.C. Diverse amide analogs of sulindac for cancer treatment and prevention. Bioorg. Med. Chem. Lett., 2017, 27, 4614-4621.
Gundogdu-Karaburun, N. Synthesis and biological activity of thiazole dithiocarbamate derivatives. Lett. Drug Des. Discov., 2014, 11, 814-823.
Koo, J. Studies in polyphosphoric acid cyclizations. J. Am. Chem. Soc., 1953, 75, 1891-1894.
Di Stefano, A.; Sozio, P.; Luisi, G.; Cacciatore, I.; Mosciatti, B.; Costa, B.; Lucacchini, A.; Martini, C.; Pinnen, F. Synthesis and preliminary pharmacological evaluation of trans-2-amino-5(6)-chloro-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes as dopamine receptor ligands. Farmaco, 2002, 57, 303-313.
Sterling, J.; Herzig, Y.; Goren, T.; Finkelstein, N.; Lerner, D.; Goldenberg, W.; Miskolczi, I.; Molnar, S.; Rantal, F.; Tamas, T.; Toth, G.; Zagyva, A.; Zekany, A.; Lavian, G.; Gross, A.; Friedman, R.; Razin, M.; Huang, W.; Krais, B.; Chorev, M.; B. Youdim, M.; Weinstock, M. Novel dual inhibitors of AChE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer’s disease. J. Med. Chem., 2002, 45, 5260-5279.
Boyd, M.R. Status of the NCI preclinical antitumor drug discovery screen. Princip. Prac. Oncol, 1989, 3, 1-12.
Monks, A.; Scudiero, D.; Skehan, P.; Shoemaker, R.; Paull, K.; Vistica, D.; Hose, C.; Langley, J.; Cronise, P.; Vaigro-Wolff, A.; Gray-Goodrich, M.; Campbell, H.; Mayo, J.; Boyd, M.J. Feasibility of a high-Flux anticancer drug screen using a diverse panel of cultured human tumor cell. J. Natl. Cancer Inst., 1991, 83, 757-766.
Boyd, M.R.; Paull, K.D. Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Dev. Res., 1995, 34, 91-109.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [111 - 118]
Pages: 8
DOI: 10.2174/1570180815666180606081042
Price: $58

Article Metrics

PDF: 34