Advertisement

Medicinal Chemistry Research

, Volume 26, Issue 11, pp 2832–2844 | Cite as

Design, synthesis, and biological evaluation of 4-H pyran derivatives as antimicrobial and anticancer agents

  • Thatikonda Narendar Reddy
  • Mettu Ravinder
  • Raktani Bikshapathi
  • Pombala Sujitha
  • C. Ganesh Kumar
  • Vaidya Jayathirtha Rao
Original Research

Abstract

A series of pyran derivatives (5–27) were synthesized in good yields by utilizing Baylis–Hillman chemistry and were further investigated for their in vitro anticancer, antibacterial, and antifungal activities. Most of the tested compounds exhibited promising antibacterial activity as compared to the standard towards Gram-positive bacterial strains. The compounds 5–7, 11–13, and 17–19 displayed two-fold higher activity whereas compound 21 showed four-fold higher antibacterial activity against Staphylococcus aureus MTCC 96 as compared to the standard Neomycin. Some of these compounds exhibited moderate antifungal activity against all the tested fungal strains. Two compounds 16 and 23 showed promising anticancer activity against selected four human cancer cell lines such as A549, DU145, HeLa, and MCF7.

Keywords

4-H pyran Baylis–Hillman reaction Antibacterial activity Antifungal activity Cytotoxicity 

Notes

Acknowledgements

The authors thank the Director, CSIR-Indian Institute of Chemical Technology for encouragement. V.J.R. thanks, CSC-0108-ORIGIN project, and  CSIR-New Delhi for Emeritus Scientist honor. T.N.R. and R.B.P. acknowledge the CSIR-UGC New Delhi, while M.R. and P.S. acknowledge the CSIR, New Delhi for research fellowships.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1982_MOESM1_ESM.doc (1.6 mb)
Supplementary Information

References

  1. Amsterdam D (1996) Susceptibility testing of antimicrobials in liquid media. In: Loman V (ed) Antibiot Lab Med, 4th edn. Williams and Wilkins, Baltimore, p 52–111Google Scholar
  2. Armaly AM, DePorre YC, Groso EJ, Riehl PS, Schindler CS (2015) Discovery of novel synthetic methodologies and reagents during natural product synthesis in the post-palytoxin era. Chem Rev 115:9232–9276CrossRefPubMedGoogle Scholar
  3. Armetso D, Horspool WM, Martin N, Ramos A, Seaone C (1989) Synthesis of cyclobutenes by the novel photochemical ring contraction of 4-substituted 2-amino-3,5-dicyano-6-phenyl-4H-pyrans. J Org Chem 54:3069–3072CrossRefGoogle Scholar
  4. Atwal KS, Rovnyak GC, Schwartz J, Moreland S, Hedberg A, Gougoutas JZ, Malley MF, Floyd DM (1990) Dihydropyrimidine calcium channel blockers: 2-heterosubstituted 4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines. J Med Chem 33:1510–1515CrossRefPubMedGoogle Scholar
  5. Basavaiah D, Dharma Rao P, Suguna Hyma R (1996) The Baylis-Hillman reaction: A novel carbon-carbon bond forming reaction. Tetrahedron 52:8001–8062CrossRefGoogle Scholar
  6. Basavaiah D, Kumaragurubaran N, Padmaja K (1999) Applications of the Baylis-Hillman adducts in organic synthesis: A facile synthesis of [E]-α-cyanocinnamyl alcohols and [E]-α-cyanocinnamic aldehydes. Synlett 1999:1630–1632CrossRefGoogle Scholar
  7. Basavaiah D, Rao AJ, Satyanarayana T (2003) Recent advances in the Baylis−Hillman reaction and applications. Chem Rev 103:811–892CrossRefPubMedGoogle Scholar
  8. Basavaiah D, Reddy BS, Badsara SS (2010) Recent contributions from the Baylis−Hillman reaction to organic chemistry. Chem Rev 110:5447–5674CrossRefPubMedGoogle Scholar
  9. Bensoussan C, Rival N, Hanquet G, Colobert F, Reymond S, Cossy J (2013) Iron-catalyzed cross-coupling between C-bromo mannopyranoside derivatives and a vinyl Grignard reagent: toward the synthesis of the C31-C52 fragment of amphidinol 3. Tetrahedron 69:7759–7770CrossRefGoogle Scholar
  10. Bharath Kumar S, Ravinder M, Kishore G, Jayathirtha Rao V, Yogeeswari P, Sriram D (2014) Synthesis, antitubercular and anticancer activity of new Baylis–Hillman adduct-derived N-cinnamyl-substituted isatin derivatives. Med Chem Res 23:1934–1940CrossRefGoogle Scholar
  11. Bhattacharyya P, Pradhan K, Paul S, Das AR (2012) Nano crystalline ZnO catalyzed one pot multicomponent reaction for an easy access of fully decorated 4H-pyran scaffolds and its rearrangement to 2-pyridone nucleus in aqueous media. Tetrahedron Lett 53:4687–4691CrossRefGoogle Scholar
  12. Bonsignore L, Loy G, Secci D, Calignano A (1993) Synthesis and pharmacological activity of 2-oxo-(2H) 1-benzopyran-3-carboxamide derivatives. Eur J Med Chem 28:517–520CrossRefGoogle Scholar
  13. Ciller JA, Martin N, Seoane C, Soto JL (1985) Ring transformation of isoxazoles into furan and pyran derivatives. J Chem Soc Perkin Trans 1:2581–2584CrossRefGoogle Scholar
  14. Drewes SE, Roos GHP (1988) Synthetic potential of the tertiary-amine-catalysed reaction of activated vinyl carbanions with aldehydes. Tetrahedron 44:653–4670CrossRefGoogle Scholar
  15. Foye WO (1991) Prinicipil di Chemico Farmaceutica. Piccin, Padova, p 416Google Scholar
  16. Gourdeau H, Leblond L, Hamelin B, Desputeau C, Dong K, Kianicka I, Custeau D, Bourdeau C, Geerts L, Cai SX, Drewe J, Labrecque D, Kasibhatla S, Tseng B (2004) Antivascular and antitumor evaluation of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes, a novel series of anticancer agents. Mol Cancer Ther 3:1375–1383PubMedGoogle Scholar
  17. Green GR, Evans, JM, Vong AK (1995) Pyrans and their benzo derivatives synthesis. In: Katritzky AR, Rees CW, Scriven EFV (eds) Comprehensive heterocyclic chemistry II, vol 5. Pergamon Press, Oxford, UK. p 469.Google Scholar
  18. Guo Z, Zhu W, Tian H (2012) Dicyanomethylene-4H-pyran chromophores for OLED emitters, logic gates and optical chemosensors. Chem Commun 48:6073–6084CrossRefGoogle Scholar
  19. Hatakeyama S, Ochi N, Numata H, Takano S (1988) A new route to substituted 3- methoxycarbonyldihydropyrans; enantioselective synthesis of (–)-methyl elenolate. J Chem Soc Chem Commun 1988:1202–1204CrossRefGoogle Scholar
  20. Hu ZP, Wang WJ, Yin XG, Zhang XJ, Yan M (2012) Enantioselective synthesis of 2-amino-4H-pyrans via the organocatalytic cascade reaction of malononitrile and α-substituted. Tetrahedron 23:461–467CrossRefGoogle Scholar
  21. Kang S, Cooper G, Dunne SF, Luan CH, Surmeier DJ, Silverman RB (2013) Antagonism of L-type Ca2+ channels CaV1.3 and CaV1.2 by 1,4-dihydropyrimidines and 4H-pyrans as dihydropyridine mimics. Bioorg Med Chem 21:4365–4373CrossRefPubMedGoogle Scholar
  22. Kappe CO (1998) 4-Aryldihydropyrimidines via the biginelli condensation: aza-analogs of nifedipine-type calcium channel modulators. Molecules 3:1–9CrossRefGoogle Scholar
  23. Kemnitzer W, Drewe J, Jiang S, Zhang H, Crogan-Grundy C, Labreque D, Bubenick M, Attardo G, Denis R, Lamothe S, gourdeau H, Tseng B, Kasibhatla S, Cai SX (2008) Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high throughput screening assay. 4. Structure–activity relationships of N-alkyl substituted pyrrole fused at the 7,8-positions. J Med Chem 51:417–423CrossRefPubMedGoogle Scholar
  24. Kemnitzer W, Drewe J, Jiang S, Zhang H, Wang Y, Zhao J, Jia S, Herich J, Labreque D, Storer R, Meerovitch K, Bouffard D, Rej R, Denis R, Blais C, Lamothe S, Attardo G, Gourdeau H, Tseng B, Kasibhatla S, Cai SX (2004) Discovery of 4-aryl-4Hchromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 1. Structure-activity relationships of the 4-aryl group. J Med Chem 47:6299–6310CrossRefPubMedGoogle Scholar
  25. Kumar D, Reddy VB, Sharad S, Dude U, Kapur S (2009) A facile one-pot green synthesis and antibacterial activity of 2-amino-4H-pyrans and 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromenes. Eur J Med Chem 44:3805–3809CrossRefPubMedGoogle Scholar
  26. Lee KH, Kim SM, Kim JY, Kim YK, Yoon SS (2010) Red fluorescent organic light-emitting diodes using modified pyran-containing DCJTB derivatives. Bull Korean Chem Soc 31:2884–2888CrossRefGoogle Scholar
  27. Lin Z, Zhang X, You X, Gao Y (2012) Facile cleavage of C–C bond: conversion of pyran derivative to 1,3-oxazin derivative. Tetrahedron 68:6759–6764CrossRefGoogle Scholar
  28. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Meth 65:55–63CrossRefGoogle Scholar
  29. Narendar Reddy T, Ravinder M, Bagul P, Ravikanti K, Bagul C, Nanubolu JB, Srinivas K, Banerjee SK, Jayathirtha Rao V (2014) Synthesis and biological evaluation of new epalrestat analogues as aldose reductase inhibitors (ARIs). Eur J Med Chem 71:53–66CrossRefGoogle Scholar
  30. Narender P, Gangadasu B, Ravinder M, Srinivas U, Swamy GYSK, Ravi kumar K, Jayathirtha Rao V (2006) Baylis–Hillman adducts between pyridine carboxaldehyde derivatives and cyclic enones. Tetrahedron 62:954–959CrossRefGoogle Scholar
  31. Narender P, Srinivas U, Ravinder M, Ramesh Ch, Rao BA, Harakishore K, Gangadasu B, Murthy USN, Jayathirtha Rao V (2006) Synthesis of multisubstituted quinolines from Baylis–Hillman adducts obtained from substituted 2-chloronicotinaldehydes and their antimicrobial activity. Bioorg Med Chem 14:4600–4609CrossRefPubMedGoogle Scholar
  32. Pavan Kumar ChNSS, Parida DK, Santhoshi A, Kota AK, Sridhar B, Jayathirtha Rao V (2011) Synthesis and biological evaluation of tetrazole containing compounds as possible anticancer agents. Med Chem Comm 2:486–492CrossRefGoogle Scholar
  33. Pettit GR, Cichacz ZA, Gao F, Herald CL, Boyd MR, Schmidt JM, Hooperlc JNA (1993) Antineoplastic agents. 257. Isolation and structure of spongistatin 1. J Org Chem 58:1302–1304CrossRefGoogle Scholar
  34. Quintela JM, Peinador C, Moreira MJ (1995) A novel synthesis of pyrano[2,3-d]pyrimidine derivatives. Tetrahedron 51:5901–5912CrossRefGoogle Scholar
  35. Ramasatyaveni G, Jagadeesh Kumar G, Mahender B, Sridhar B, Jayathirtha Rao V, Das A (2016) 2-Azetidinones: Synthesis and biological evaluation as potential antibreast cancer agents. Eur J Med Chem 124:544–558CrossRefGoogle Scholar
  36. Ravinder M, Mahendar B, Saidulu M, Hamsini KV, Narendar Reddy T, Rohit Ch, Sanjay Kumar B, Srinivas K, Jayathirtha Rao V (2012) Synthesis and evaluation of novel 2-pyridone derivatives as inhibitors of phosphodiesterase3 (PDE3): A target for heart failure and platelet aggregation. Bioorg Med Chem Lett 22:6010–6015CrossRefPubMedGoogle Scholar
  37. Ravinder M, Sadhu PS, Jayathirtha Rao V (2009) Simple, facile and one-pot conversion of the Baylis–Hillman acetates into 3,5,6-trisubstituted-2-pyridones. Tetrahedron Lett 50:4229–4232CrossRefGoogle Scholar
  38. Ravinder M, Sadhu PS, Santhoshi A, Narender P, Swamy GYSK, Ravikumar D, Jayathirtha Rao V (2010) Synthesis of new aminonicotinate derivatives from acetylated Baylis-Hillman adducts and enamino esters via a consecutive [3+3]-annulation protocol. Synthesis pp 573–578Google Scholar
  39. Singh V, Batra S (2008) Advances in the Baylis–Hillman reaction-assisted synthesis of cyclic frameworks. Tetrahedron 64:4511–4574CrossRefGoogle Scholar
  40. Smith III AB, Corbett RM, Pettit GR, Chapuis JC, Schmidt JM, Hamel E, Jung MK (2002) Synthesis and biological evaluation of a spongistatin AB-spiroketal analogue. Bioorg Med Chem Lett 12:2039–2042CrossRefPubMedGoogle Scholar
  41. Smith PW, Sollis SL, Howes PD, Cherry PC, Starkey ID, Cobley KN, Weston H, Scicinski J, Merritt A, Whittington A, Wyatt P, Taylor N, Green D, Bethell R, Madar S, Fenton RJ, Morley PJ, Pateman T, Beresford A (1998) Dihydropyrancarboxamides related to zanamivir: A new series of inhibitors of influenza virus sialidases. 1. Discovery, synthesis, biological activity, and structure-activity relationships of 4-guanidino- and 4-amino-4H-pyran-6-carboxamides. J Med Chem 41:787–797CrossRefPubMedGoogle Scholar
  42. Uckun FM, Mao C, Vassilev AO, Huang H, Jan ST (2000) Structure-based design of a novel synthetic spiroketal pyran as a pharmacophore for the marine natural product spongistatin 1. Bioorg Med Chem Lett 10:541–545CrossRefPubMedGoogle Scholar
  43. Urbahns K, Horváth E, Stasch JP, Mauler F (2003) 4-Phenyl-4H-pyrans as IKca channel blockers. Bioorg Med Chem Lett 13:2637–2639CrossRefPubMedGoogle Scholar
  44. Wyatt PG, Coomber BA, Evans DN, Jack TI, Fulton HE, Wonacott AJ, Colman P, Varghese J (2001) Sialidase inhibitors related to zanamivir. Further SAR studies of 4-amino-4H-pyran-2-carboxylic acid-6-propylamides. Bioorg Med Chem Let 11:669–673CrossRefGoogle Scholar
  45. Yadav LDS, Srivastava VP, Patel R (2008) Ionic liquid [Hmim]HSO4-promoted one-pot oxidative conjugate addition of sulfur-centred nucleophiles to Baylis–Hillman adducts. Tetrahedron Lett 49:3142–3146CrossRefGoogle Scholar
  46. Zhang YL, Chen BZ, Zheng KQ, Xu ML, Lei XH (1982) Chinese Acta Pharmaceutica Sinica, 17. Chem Abstr 96:135383eGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Crop Protection Chemicals DivisionCSIR-Indian Institute of Chemical TechnologyHyderabadIndia
  2. 2.Medicinal Chemistry and Pharmacology DivisionCSIR-Indian Institute of Chemical TechnologyHyderabadIndia
  3. 3.Academy of Scientific and Innovation ResearchCSIR-Indian Institute of Chemical TechnologyHyderabadIndia

Personalised recommendations