Abstract
The present work reports the synthesis of novel 5-Oxo-5,6,7,8-tetrahydroquinoline and 2,5-dioxo-5,6,7,8-tetrahydroquinoline derivatives containing enaminone system and bearing a sulfonamide moiety. The newly synthesized compounds were designed in compliance with the general pharmacophoric requirements for carbonic anhydrase inhibiting anticancer drugs, as this may play a role in their anticancer activity. Twelve of the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Compounds 5c, 7, 10, and 12c showed IC50 values (0.048, 0.040, 0.041, 0.044 μM, respectively) comparable to that of the reference drug doxorubicin (IC50 = 0.04 μM). On the other hand, compounds 12a, 12d, and 16b exhibited better activity than doxorubicin with an IC50 values (0.025, 0.036, 0.015 μM, respectively).
Similar content being viewed by others
References
Abbas EMH, Farghaly TA (2010) Synthesis, reactions, and biological activity of 1,4-benzothiazine derivatives. Monatsh Chem 141:661–667
Ahmed N, Brahmbhatt KG, Sabde S, Mitra D, Singh IP, Bhutani KK (2010) Synthesis and anti-HIV activity of alkylated quinoline 2,4-diols. Bioorg Med Chem 18:2872–2879
Alqasoumi SI, Al-Taweel AM, Alafeefy AM, Ghorab MM, Noaman E (2010b) Discovering some novel tetrahydroquinoline derivatives bearing the biologically active sulfonamide moiety as a new class of antitumor agents. Eur J Med Chem 45:1849–1853
Alqasoumi SI, Al-Taweel AM, Alafeefy AM, Hamed MM, Noaman E, Ghorab MM (2009) Synthesis and biological evaluation of 2-Amino-7,7-dimethyl4-substituted-5-oxo-1-(3,4,5-trimethoxy)-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile derivatives as potential cytotoxic agents. Bioorg Med Chem Lett 19:6939–6942
Alqasoumi SI, Al-Taweel AM, Alafeefy AM, Noaman E, Ghorab MM (2010a) Novel quinolines and pyrimido[4,5-b]quinolines bearing biologically active sulfonamide moiety as a new class of antitumor agents. Eur J Med Chem 45:738–744
Al-Said MS, Ghorab MM, Al-Dosari MS, Hamed MM (2011) Synthesis and In-vitro anticancer evaluation of some novel hexahydroquinoline derivatives having a benzenesulfonamide moiety. Eur J Med Chem 46:201–207
Carta A, Briguglio I, Piras S, Corona P, Boatto G, Nieddu M, Giunchedi P, Marongiu ME, Giliberti G, Iuliano F, Blois S, Ibba C, Busonera B, Colla PL (2011) Quinoline tricyclic derivatives. Design, synthesis and evaluation of the antiviral activity of three new classes of RNA-dependent RNA polymerase inhibitors. Bioorg Med Chem 19:7070–7084
Chen Z, W Y, Liu Y, Yu L, Zhou L, Yang S, Lai L (2011) Quinoline-4-methyl esters as human nonpancreatic secretory phospholipase A2 inhibitors. Bioorg Med Chem 19:3361–3366
Creaven BS, Duff B, Egan DA, Kavanagh K, Rosair G, Thangella VR, Walsh M (2010) Anticancer and antifungal activity of Copper(II) complexes of quinolin-2(1H)-one-derived schiff bases. Inorg Chim Acta 363:4048–4058
Daniel L (2007) The organic chemistry of drug synthesis. Wiley, Hoboken, pp 167–171
Edafiogho IO, Phillips OA, Udo EE, Samuel S, Rethish B (2009) Synthesis, antibacterial and anticonvulsant evaluations of some cyclic enaminones. Eur J Med Chem 44:967–975
Eddington ND, Cox DS, Roberts RR, Butcher RJ, Edafiogho IO, Stables JP, Cooke N, Goodwin AM, Smith CA, Scott KR (2002) Synthesis and anticonvulsant activity of enaminones. 4. Investigations on isoxazole derivatives. Eur J Med Chem 37:635–648
Eddington ND, Cox DS, Roberts RR, Stables JP, Powell CB, Scott KR (2000) Enaminones-versatile therapeutic pharmacophores. Further advances. Curr Med Chem 7:417–436
El-Hashim A, Yousefi S, Edafiogho I, Raghupathy R, Yousif M, Simon HU (2010) Anti-inflammatory and immunosuppressive effects of the Enaminone E121. Eur J Pharmacol 632:73–78
El-Hashim AZ, Edafiogho IO, Jaffal SM (2001) Anti-tussive and Bronchodilator mechanisms of action for the Enaminone E121. Life Sci 89:378–387
El-Sabbagh OI, Rady HM (2009) Synthesis of new acridines and hydrazones derived from cyclic β-diketone for cytotoxic and antiviral evaluation. Eur J Med Chem 44:3680–3686
El-Sabbagh OI, Shabaan MA, Kadry HH, Saad Al-Din E (2010) New octahydroquinazoline derivatives: synthesis and hypotensive activity. Eur J Med Chem 45:5390–5396
Gao M, Wang M, Miller KD, Hutchins GD, Zheng QH (2010) Synthesis and in-vitro biological evaluation of carbon-11-labeled quinoline derivatives as new candidate PET radioligands for cannabinoid CB2 receptor imaging. Bioorg Med Chem 18:2099–2106
García GC, Bejarano BP, Ruiz IL, Nieto MA´G (2012) Comparison of representational spaces based on structural information in the development of QSAR models for benzylamino enaminone derivatives. SAR QSAR Environ Res 23:751–774
Garudachari B, Satyanarayana MN, Thippeswamy B, Shivakumar CK, Shivananda KN, Hegde G, Isloor AM (2012) Synthesis, characterization and antimicrobial studies of some new quinoline incorporated benzimidazole derivatives. Eur J Med Chem 54:900–906
Ghodsi R, Zarghi A, Daraei B, Hedayati M (2010) Design, synthesis and biological evaluation of new 2,3-diarylquinoline derivatives as selective cyclooxygenase-2 inhibitors. Bioorg Med Chem 18:1029–1033
Ghorab MM, Ragab FA, Heiba HI, Arafa RK, El-Hossary EM (2010) In-vitro anticancer screening and radiosensitizing evaluation of some new quinolines and pyrimido[4,5-b]quinolines bearing a sulfonamide moiety. Eur J Med Chem 45:3677–3684
Ghorab MM, Ragab FA, Noaman E, Heiba HI, El-Hossary EM (2009) Synthesis of some novel quinolines and pyrimido [4,5-b] quinolines bearing a sulphonamide moiety as potential anticancer and radioactive agents. Drug Res 57:795–803
Guo RH, Zhang Q, Maa YB, Huang XY, Luo J, Wang LJ, Geng CA, Zhang XM, Zhou J, Jiang ZY, Chen JJ (2011) Synthesis and biological assay of 4-aryl-6-chloro-quinoline derivatives as novel non-nucleoside anti-HBV agents. Bioorg Med Chem 19:1400–1408
Jackson PL, Hanson CD, Farrell AK, Butcher RJ, Stables JP, Eddington ND, Scott KR (2012) Enaminones 12. An explanation of anticonvulsant activity and toxicity per linus pauling’s clathrate hypothesis. Eur J Med Chem 51:42–51
Jayagobi M, Raghunathan R, Sainath S, Raghunathan M (2011) Synthesis and antibacterial property of pyrrolopyrano quinolinones and pyrroloquinolines. Eur J Med Chem 46:2075–2082
Korrichi L, Dalila B, Dalila S (2009) Quinolines antioxydant activity structure activity relationship. Eur J Bio Sci 1:32–36
Kouznetsov VV, Gómez CMM, Derita MG, Svetaz L, Olmo Ed, Zacchino SA (2012) Synthesis and antifungal activity of diverse C-2 pyridinyl and pyridinylvinyl substituted quinolines. Bioorg Med Chem 20:6506–6512
Kumar KS, Kumar SK, Sreenivas BY, Gorja DR, Kapavarapu R, Rambabu D, Krishna GR, Reddy CM, Rao MVB, Parsa KVL, Pal M (2012) C–C bond formation at C-2 of a quinoline ring: synthesis of 2-(1H-indol-3-yl) quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors. Bioorg Med Chem 20:2199–2207
Lu CM, Chen YL, Chen HL, Chen CA, Lu PJ, Yang CN, Tzeng CC (2010) Synthesis and antiproliferative evaluation of certain Indolo[3,2-c]quinoline derivatives. Bioorg Med Chem 18:1948–1957
Makawana JA, Patel MP, Patel RG (2012) Synthesis and in-vitro antimicrobial activity of N-arylquinoline derivatives bearing 2-morpholinoquinoline moiety. Chin Chem Lett 23:427–430
Michael J, de Koning C, Gravestock D, Hosken G, Howard A, Jungmann C, Krause R, Parsons A, Pelly S, Stanbury T (1999) Enaminones: versatile intermediates for natural product synthesis. Pure Appl Chem 71:979–988
Perin N, Uzelac L, Piantanida I, Zamola GK, Kralj M, Hranjec M (2011) Novel biologically active nitro and amino substituted benzimidazo [1,2-a]quinolines. Bioorg Med Chem 19:6329–6339
Pretorius SI, Breytenbach WJ, Kock Cd, Smith PJ, N’Da DD (2013) Synthesis, characterization and antimalarial activity of quinoline–pyrimidine hybrids. Bioorg Med Chem 21:269–277
Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer 82:1107–1112
Supuran CT, Scozzafava A, Casini A (2003) Carbonic anhydrase inhibitors. Med Res Rev 23:146–189
Thiry A, Ledecq M, Cecchi A, Dogne JM, Wouters J, Supuran CT, Masereel B (2006) Indanesulfonamides as carbonic anhydrase inhibitors. Toward structure-based design of selective inhibitors of the tumor-associated isozyme CA IX. J Med Chem 49:2743–2749
Vandurm P, Cauvin C, Guiguen A, Georges B, Van KL, Martinelli V, Cardona C, Mbemba G, Mouscadet JF, Hevesi L, Lint CV, Wouters J (2009) Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor. Bioorg Med Chem Lett 19:4806–4809
Wang L, witalska M, Mei ZW, Lu WJ, Takahara Y, Feng XW, El-Sayed I, Wietrzyk J, Inokuchi T (2012) Synthesis and in-vitro Antiproliferative activity of new 11-aminoalkylamino-substituted 5H- and 6H-Indolo[2,3-b]quinolines; structure activity relationships of neocryptolepines and 6-methyl congeners. Bioorg Med Chem 20:4820–4829
Acknowledgements
The authors acknowledge with thanks the NMR unit at King Abdulaziz University for their technical support.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Ahmed, N.S., Badahdah, K.O. & Qassar, H.M. Novel quinoline bearing sulfonamide derivatives and their cytotoxic activity against MCF7 cell line. Med Chem Res 26, 1201–1212 (2017). https://doi.org/10.1007/s00044-017-1850-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-017-1850-9