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Synthesis, antitumor activity, and structure–activity relationship of some 4H-pyrano[3,2-h]quinoline and 7H-pyrimido[4′,5′:6,5]pyrano[3,2-h]quinoline derivatives

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Abstract

Several 4H-pyrano[3,2-h]quinoline (3a–d, 4a, 7a,b, 9a–c, 10a,b, 11a,b, and 13a–c) and 7H-pyrimido[4′,5′:6,5]pyrano[3,2-h]quinoline derivatives (8a–c) were obtained by treatment of 8-hydroxyquinoline (1a) and 8-hydroxy-2-methylquinoline (1b) with α-cyano-p-chloro/bromocinnamonitrile (2a,b) or 4H-pyrano[3,2-h]quinoline derivatives (3a,c,d) with different electrophilic reagents followed by nucleophilic reagents. Structures of these compounds were established on the basis of spectral data. The antitumor activity of the synthesized compounds was investigated in comparison with Vinblastine. Among them, compounds 3c,d, 4a, 8b, 9b,c, 11a,b, and 13a,c inhibited the growth of cancer cells compared to Vinblastine. The structure–activity relationships were discussed.

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References

  • Abd-El-Aziz AS, El-Agrody AM, Bedair AH, Christopher Corkery T, Ata A (2004) Synthesis of hydroxyquinoline derivatives, aminohydroxychromene, aminocoumarin and their antimicrobial activities. Heterocycles 63:1793–1812

    Article  CAS  Google Scholar 

  • Abd-El-Aziz AS, Mohamed HM, Mohammed S, Zahid S, Ata A, Bedair AH, El-Agrody AM, Harvey PD (2007) Synthesis of novel coumarin and benzocoumarin derivatives and their biological and photophysical studies. J Heterocycl Chem 44:1287–1300

    Article  CAS  Google Scholar 

  • Al-Ghamdi AM, Abd EL-Wahab AHF, Mohamed HM, El-Agrody AM (2012) Synthesis and antitumor activities of 4H-pyrano[3,2-h]quinoline-3-carbonitrile, 7H-pyrimido-[4’,5′:6,5]pyrano[3,2-h]quinoline, and 14H-pyrimido[4′,5′:6,5]pyrano[3,2-h][1,2,4]-triazolo[1,5-c]quinoline derivatives. Lett Drug Des Discov 9:459–470

    CAS  Google Scholar 

  • Andrew T, Marilena V, Maria G, Aphrodite E, Constantine I, Anna K, Pandelis AA, Dimitri M, Christos R (2007) Symmetrical derivatives of C2-substituted pyrrolo[2,3-f]-quinolines: synthesis, cytotoxicity and drug delivery studies. Lett Drug Des Discov 4:87–91

    Article  Google Scholar 

  • Badawey ES, Kappe T (1997) Potential antineoplastics. Synthesis and cytotoxicity of certain 4-chloro-3-(2-chloroethyl)-2-methylquinolines and related derivatives. Eur J Med Chem 32:815–822

    Article  CAS  Google Scholar 

  • Bedair AH, El-Hady NA, Abd El-Latif MS, Fakery AH, El-Agrody AM (2000) 4-Hydroxycoumarin in heterocyclic synthesis part III: synthesis of some new pyrano[2,3-d]pyrimidine, 2-substituted[1,2,4]triazolo[1,5-c]pyrimidine and pyrimido[1,6-b][1,2,4]triazine derivatives. IL Farmaco 55:708–714

    Article  PubMed  CAS  Google Scholar 

  • Bedair AH, Emam HA, El-Hady NA, Ahmed KAR, El-Agrody AM (2001) Synthesis and antimicrobial activities of novel naphtho[2,1-b]pyran, pyrano[3,2-d]pyrimidine and pyrano[3,2-e][1,2,4]triazolo[2,3-c]pyrimidine derivatives. IL Farmaco 56:965–973

    Article  PubMed  CAS  Google Scholar 

  • Broch S, Hénon H, Debaud AL, Fogeron ML, Bonnefoy-Bérard N, Anizon F, Moreau P (2010) Synthesis and biological activities of new di- and trimeric quinoline derivatives. Bioorg Med Chem 18:7132–7143

    Article  PubMed  CAS  Google Scholar 

  • Chang FS, Chen W, Wangb C, Tzeng CC, Chen YL (2010) Synthesis and antiproliferative evaluations of certain 2-phenylvinylquinoline (2-styrylquinoline) and 2-furanylvinyl-quinoline derivatives. Bioorg Med Chem 18:124–132

    Article  PubMed  CAS  Google Scholar 

  • Desai NC, Dodiya AM (2011) Conventional and microwave techniques for synthesis and antimicrobial studies of novel 1-[2-(2-chloro(3-quinolyl))-5-(4-nitrophenyl)-(1,3,4-oxadiazolin-3-yl)]-3-(aryl)prop-2-en-1-ones. Med Chem Res. doi:10.1007/s00044-011-9670-9

  • Eid FA, Bedair AH, Emam HA, Mohamed HM, El-Agrody AM (2003) Reaction of activated nitriles with methanolic piperidine and synthesis of 1h-benzo[f]chromene, diazabenzo[j]anthracene and diazabenzo[a][1,2,4]triazolo[j]anthracene derivatives. Al-Azhar Bull Sci 14:311–342

    Google Scholar 

  • El-Agrody AM (1994) Condensation reactions of α-cyanocinnamonitriles with naphthols: synthesis of naphthopyranopyrimidines and a naphthopyranone. J Chem Res (S) 280–281

  • El-Agrody AM, Al-Ghamdi AM (2011) Synthesis of certain novel 4H-pyrano[3,2-h]quinoline derivatives. Arkivoc xi:134–46

  • El-Agrody AM, Emam HA, El-Hakim MH, Abd El-Latif MS, Fakery AH (1997a) Activated nitriles in heterocyclic synthesis: synthesis of pyrano[3,2-d]pyrimidine and pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives. J Chem Res (S) 320–321

  • El-Agrody AM, Emam HA, El-Hakim MH, Abd El-Latif MS, Fakery AH (1997b) Activated nitriles in heterocyclic synthesis: synthesis of pyrano[3,2-d]pyrimidine and pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives. J Chem Res (M) 2039–2048

  • El-Agrody AM, El-Hakim MH, Abd El-Latif MS, Fakery AH, El-Sayed ESM, El-Ghareab KA (2000) Synthesis of pyrano[2,3-d]pyrimidine and pyrano[3,2-e][1,2,4]triazolo[2,3-c]-pyrimidine derivatives with promising antimicrobial activities. Acta Pharm 50:111–120

    CAS  Google Scholar 

  • El-Agrody AM, Abd El-Latif MS, El-Hady NA, Fakery AH, Bedair AH (2001) Heteroaromatization with 4-hydroxycoumarin part II: synthesis of some new pyrano[2,3-d]pyrimidine, [1,2,4]triazolo[1,5-c]pyrimidine and pyrimido[1,6-b][1,2,4]-triazine derivatives. Molecules 6:519–527

    Article  CAS  Google Scholar 

  • El-Agrody AM, Eid FA, Emam HA, Mohamed HM, Bedair AH (2002) Synthesis of 9-methoxy and 9-acetoxy-3-amino-1-(4-methoxyphenyl)-1H-benzo[f]chromene-2-carbonitriles via 2-(iminopiperidin-1-yl-methyl)-3-(4-methoxyphenyl)acrylonitrile as intermediate. Z Naturforsch Teil B 57:579–585

    CAS  Google Scholar 

  • El-Agrody AM, Sabry NM, Motlaq SS (2011) Synthesis of some new 2-substituted 12H-chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine, 3-ethoxycarbonyl-12H-chromeno[3,2-e]-[1,2,4]triazolo[1,5-c]pyrimidine-2-one, ethyl 2-formylamino\acetylamino-4H-chromene-3-carboxylate and some of their antimicrobial activities. J Chem Res 35:77–83

    Article  CAS  Google Scholar 

  • El-Agrody AM, Khattab ESAEH, Fouda AM, Al-Ghamdi AM (2012) Synthesis, antimicrobial and antitumor activities of certain novel 2-amino-9-(4-halostyryl)-4H-pyrano[3,2-h]-quinoline derivatives. Med Chem Res. doi:10.1007/s00044-011-9965-x

  • Ganesh T, Min J, Thepchatri P, Du Y, Li L, Lewis I, Wilson L, Chiosis HFG, Dingledine R, Liotta D, Snyder JP, Sun A (2008) Discovery of aminoquinolines as a new class of potent inhibitors of heat shock protein 90 (Hsp90): synthesis, biology, and molecular modeling. Bioorg Med Chem 16:6903–6910

    Article  PubMed  CAS  Google Scholar 

  • Guo RH, Zhang Q, Ma 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-chloroquinoline derivatives as novel non-nucleoside anti-HBV agents. Bioorg Med Chem 19:1400–1408

    Article  PubMed  CAS  Google Scholar 

  • Harris CR, Thorarensen A (2004) Advances in the discovery of novel antibacterial agents during the year 2002. Curr Med Chem 11:2213–2243

    Article  PubMed  CAS  Google Scholar 

  • Jampilek J, Musiol R, Pesko M, Kralova K, Vejsova M, Carroll J, Coffey A, Finster J, Tabak D, Niedbala H, Kozik V, Polanski J, Csollei J, Dohnal J (2009) Ring-substituted 4-hydroxy-1H-quinolin-2-ones: preparation and biological activity. Molecules 14:1145–1159

    Article  PubMed  CAS  Google Scholar 

  • Khafagy MM, Abd El-Wahab AHF, Eid FA, El-Agrody AM (2002) Synthesis of halogen derivatives of benzo[h]cheromene and benzo[a]anthracene with promising antimicrobial activities. IL Farmaco 57:715–722

    Article  PubMed  CAS  Google Scholar 

  • Larghi EL, Bohn ML, Kaufman TS (2009) Aaptamine and related products. Their isolation, chemical syntheses and biological activity. Tetrahedron 65:4257–4282

    Article  CAS  Google Scholar 

  • Mossman T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  Google Scholar 

  • Mrozek-Wilczkiewicz A, Kalinowski DS, Musiol R, Finster J, Szurko A, Serafin K, Knas M, Kamalapuram SK, Kovacevic Z, Jampilek J, Ratuszna A, Rzeszowska-Wolny J, Richardson DR, Polanski J (2010) Investigating the anti-proliferative activity of styrylazanaphthalenes and azanaphthalenediones. Bioorg Med Chem 18:2664–2671

    Article  PubMed  CAS  Google Scholar 

  • Musiol R, Jampilek J, Buchta V, Silva L, Niedbala H, Podeszwa B, Palka A, Majerz-Maniecka K, Oleksyn B, Polanski J (2006) Antifungal properties of new series of quinoline derivatives. Bioorg Med Chem 14:3592–3598

    Article  PubMed  CAS  Google Scholar 

  • Musiol R, Jampilek J, Kralova K, Richardson DR, Finster J, Kalinowski D, Podeszwa B, Niedbala H, Palka A, Polanski J (2007) Investigating biological activity spectrum for novel quinoline analogues. Bioorg Med Chem 15:1280–1288

    Article  PubMed  CAS  Google Scholar 

  • Musiol R, Tabak D, Niedbala H, Podeszwa B, Jampilek J, Kralova K, Dohnal J, Finster J, Mencel A, Polanski J (2008) Investigating biological activity spectrum for novel quinoline analogues 2: hydroxyquinolinecarboxamides with photosynthesis-inhibiting activity. Bioorg Med Chem 16:4490–4499

    Article  PubMed  CAS  Google Scholar 

  • Narender P, Srinivas U, Ravinder MCh, Ramesh BK, Gangadasu B, Murthy USN, Jayathirtha RV (2006) Synthesis of multisubstituted quinolines from Baylis–Hillman adducts obtained from substituted 2-chloronicotinaldehydes and their antimicrobial activity. Bioorg Med Chem 14:4600–4609

    Article  PubMed  CAS  Google Scholar 

  • Pommier Y, Johnson AA, Marchand C (2005) Integrase inhibitors to treat HIV/Aids. Nat Rev Drug Discov 4:236–248

    Article  PubMed  CAS  Google Scholar 

  • Rahman AU, Choudhary MI, Thomsen WJ (2001) Bioassay technique for drug development. Harwood Academic Publishers, Chur

    Book  Google Scholar 

  • Ramesh RD, Manian RS, Raghunathan R, Sainath S, Raghunathan M (2009) Synthesis and antibacterial property of quinolines with potent DNA gyrase activity. Bioorg Med Chem 17:660–666

    Article  PubMed  CAS  Google Scholar 

  • Righi G, Ciambrone S, Bonini C, Campaner P (2008) Stereocontrolled synthesis and biological activity of two diastereoisomers of the potent HIV-1 protease inhibitor saquinavir. Bioorg Med Chem 16:902–908

    Article  PubMed  CAS  Google Scholar 

  • Sabry NM, Mohamed HM, Khattab Essam Shawky AEH, Motlaq SS, El-Agrody AM (2011) Synthesis of 4H-chromene, coumarin, 12H-chromeno[2,3-d]pyrimidine derivatives and some of their antimicrobial and cytotoxicity activities. Eur J Med Chem 46:765–772

    Article  PubMed  CAS  Google Scholar 

  • Salaheldin AM, Oliveira-Campos AMF, Rodrigues L (2008) 3-Aminopyrroles and their application in the synthesis of pyrrolo[3,2-d]pyrimidine (9-deazapurine) derivatives. Arkivoc xiv:180–190

  • Saugues E, Nauton L, Théry V, Anizon F, Moreau P (2011) Synthesis and molecular modeling study of new trimeric quinoline derivatives. Bioorg Chem 39:143–150

    Article  PubMed  CAS  Google Scholar 

  • Sayed AZ, El-Hady NA, El-Agrody AM (2000) Condensation of α-cyanocinnamonitriles with 6-bromo-2-naphthols: synthesis of pyrano[2,3-d]pyrimidine and pyrano[3,2-e][1,2,4]-triazolo[2,3-c]pyrimidine derivatives. J Chem Res 164–166

  • Tacconi G, Gatti G, Desimoni G, Messori V (1980) A new route to 4H-pyrano[2, 3-c]pyrazoles. J Prakt Chem 322:831–834

    Article  CAS  Google Scholar 

  • Thomas LJ, Roy K (2008) Exploring molecular shape analysis of styrylquinoline derivatives as HIV-1 integrase inhibitors. Eur J Med Chem 43:81–92

    Article  Google Scholar 

  • Thomas KD, Adhikari AV, Shetty NS (2010) Design, synthesis and antimicrobial activities of some new quinoline derivatives carrying 1,2,3-triazole moiety. Eur J Med Chem 45:3803–3810

    Article  PubMed  CAS  Google Scholar 

  • **n-Hua L, **g Z, An-na Z, Bao-An S, Hai-Liang Z, Lin-Shan b, Pinaki SB, Chun-**u P (2009) Synthesis, structure and antibacterial activity of new 2-(1-(2-(substituted-phenyl)-5-methyloxazol-4-yl)-3-(2-substitued-phenyl)-4,5-dihydro-1H-pyrazol-5-yl)-7-substitued-1,2,3,4-tetrahydroisoquinoline derivatives. Bioorg Med Chem 17:1207–1213

    Article  Google Scholar 

  • Zouhiri F, Danet M, Bernard C, Normand-Bayle M, Mouscadet JF, Leh H, Thomas CM, Mbemba G, d’Angelo J, Desmaele D (2005) HIV-1 replication inhibitors of the styrylquinoline class: introduction of an additional carboxyl group at the C-5 position of the quinoline. Tetrahedron Lett 46:2201–2205

    Article  CAS  Google Scholar 

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Acknowledgments

This study was supported by King Abdulaziz City for Science and Technology (KACST), No. A-S-11-0560. The authors deeply thank the Regional Center for Mycology & Biotechnology (RCMP), Al-Azhar University for carrying out the antitumor study and Mr. Ali Y. A. Alshahrani for making the 1H NMR and 13C NMR samples.

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  1. Chemistry Department, Faculty of Science, King Khalid University, Abha, 9004, Saudi Arabia

    Ahmed M. El-Agrody, Hisham S. M. Abd-Rabboh & Abdullah M. Al-Ghamdi

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  1. Ahmed M. El-Agrody
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  2. Hisham S. M. Abd-Rabboh
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  3. Abdullah M. Al-Ghamdi
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Correspondence to Ahmed M. El-Agrody.

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El-Agrody, A.M., Abd-Rabboh, H.S.M. & Al-Ghamdi, A.M. Synthesis, antitumor activity, and structure–activity relationship of some 4H-pyrano[3,2-h]quinoline and 7H-pyrimido[4′,5′:6,5]pyrano[3,2-h]quinoline derivatives. Med Chem Res 22, 1339–1355 (2013). https://doi.org/10.1007/s00044-012-0142-7

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