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Design and synthesis of (Z/E)-2-phenyl/H-3-styryl-2H-chromene derivatives as antimicrotubule agents

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Abstract

Two new series of compounds (Z / E)-2-phenyl/H-3-Styryl-2H-Chromenes 9(a-r) and 10(a-s) were synthesized and evaluated in vitro cytotoxic activities against four cancer cell lines. One compound, (Z)-8-ethoxy-3-(4-methoxystyryl)-2-phenyl-2H-chromene ( 9g) was found to be the most active among the tested compounds in HeLa cell lines (\({\hbox {IC}}_{50} 10 {\upmu }\hbox {M}\)). Compound 9g arrested cells at G2/M phase, disrupted microtubule network, accumulated tubulin in the soluble fraction and manifested an increased expression of the G2/M marker, Cyclin B1.

Graphical Abstract

SYNOPSIS Two new series of compounds (Z / E)-2-phenyl/H-3-Styryl-2H-Chromenes (37 compounds) were synthesized and evaluated for in vitro cytotoxic activities against four cancer cell lines. One compound, (Z)-8-ethoxy-3-(4-methoxystyryl)-2-phenyl-2H-chromene ( 9g) was found to be the most active among the tested compounds in HeLa cell lines (\({\hbox {IC}}_{50} 10 {\upmu }\hbox {M}\)).

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References

  1. Rahmani-Nezhad S, Safavi M, Pordeli M, Ardestani S K, Khosravani L, Pourshojaei Y, Mahdavi M, Emami S, Foroumadi A and Shafiee A 2014 Synthesis, in vitro cytotoxicity and apoptosis inducing study of 2-aryl-3-nitro-2\(H\)-chromene derivatives as potent anti-breast cancer agents Eur. J. Med. Chem. 86 562

    Article  CAS  PubMed  Google Scholar 

  2. Kumar R N, Poornachandra Y, Nagender P, Kumar G S, Swaroop D K, Kumar C G and Narsaiah B 2016 Synthesis of novel nicotinohydrazide and (1,3,4-oxadiazol-2-yl)-6-(trifluoromethyl) pyridine derivatives as potential anticancer agents Bioorg. Med. Chem. Lett. 26 4829

    Article  CAS  Google Scholar 

  3. Siddiqui A A, Iram F, Siddiqui S and Sahu K 2014 Role of natural products in drug discovery process Int. J. Drug Dev. Res. 6 172

    CAS  Google Scholar 

  4. Carter S K, Bakowski M T and Hellman K 1989 Chemotherapy of Cancer 3\(^{\text{rd}}\) edn. (New York: Wiley & Sons)

  5. Fortin S and Berube G 2013 Advances in the development of hybrid anticancer drugs Expert Opin. Drug Discov. 8 1029

    Article  CAS  PubMed  Google Scholar 

  6. Cheenpracha S, Karalai C, Ponglimanont C and Kanjana-Opas A 2009 Candenatenins A-F, Phenolic Compounds from the Heartwood of Dalbergiacandenatensis J. Nat. Prod. 72 1395

    Article  CAS  PubMed  Google Scholar 

  7. Wang W, Ao L, Rayburn E R, Xu H, Zhang X, Zhang X, Nag S A, Wu X, Wang M H, Wang H, Van Meir E G and Zhang R 2012 KCN1, a Novel Synthetic Sulfonamide Anticancer Agent: In Vitro and In Vivo Anti-Pancreatic Cancer Activities and Preclinical Pharmacology PLoS ONE 7 44883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yin S Q, Shi M, KongT T, Zhang C M, Han K, Cao B, Zhang Z, Du X, Tang L Q, Mao X and Liu Z P 2013 Preparation of S14161 and its analogues and the discovery of 6-bromo-8-ethoxy-3-nitro-2\(H\)-chromene as a more potent antitumor agent in vitro Bioorg. Med. Chem. Lett. 23 3314

    Article  CAS  PubMed  Google Scholar 

  9. (a) Tomer E, Goren R and Monselise S P 1969 Isolation and identification of seselin in Citrus roots Phytochemistry 8 1315; (b) Nishino H, Okuyama T, Takata M, Shibata S, Tokuda H and Takayasu J 1990 Studies on the anti-tumor-promoting activity of naturally occurring substances. IV. Pd-II [(+)anomalin, (+)praeruptorin B], a seselin-type coumarin, inhibits the promotion of skin tumor formation by 12-\(O\)-tetradecanoylphorbol-13-acetate in 7,12-dimethylbenz[\(a\)]anthracene-initiated mice Carcinogenesis 11 1557

  10. (a) Cazal C M, Domingues V C, Batalhão J R, Bueno O C, Rodrigues Filho E, Silva M F G F, Vieira P C and Fernandes J B 2009 Isolation of xanthyletin, an inhibitor of ants’ symbiotic fungus, by high-speed counter-current chromatography J. Chromatogr. A 1216 4307; (b) Choi M, Hwang Y S, Kumar A S, Jo H, Jeong Y, Oh Y, Lee J, Yun J, Kim Y, Han S B, Jung J K, Cho J and Lee H 2014 Design and synthesis of 3, 4-dihydro-2H-benzo [h] chromene derivatives as potential NF-\(\kappa \)B inhibitors Bioorg. Med. Chem. Lett. 24 2404

  11. Kaouadji M, Agban A and Mariotte A M 1986 Lonchocarpene, a stilbene, and lonchocarpusone, an isoflavone: two new pyranopolyphenols from Lonchocarpusnicou roots J. Nat. Prod. 49 281

    Article  CAS  Google Scholar 

  12. (a) Beck J R, Kwok R, Booher R N, Brown A C, Patterson L E, Pranc P, Rockey B and Pohland A 1968 Synthesis of acronycine J. Amer. Chem. Soc. 90 4706; (b) Koch M 2007 From acronycine to benzo-[b]-acronycine derivatives: potent antitumor agents Bull. Acad. Natl. Med. 191 83

  13. Azizmohammadi M, Khoobi M, Ramazani A, Emami S, Zarrin A, Firuzi O, Miri R and Shafiee A 2013 2\(H\)-chromene derivatives bearing thiazolidine-2, 4-dione, rhodanine or hydantoin moieties as potential anticancer agents Eur. J. Med. Chem. 59 15

    Article  CAS  PubMed  Google Scholar 

  14. Jakubowska J, MikuBa-Pietrasik J, Ksidhek K and Krawczyk H 2014 Cytotoxicity studies of novel combretastatin and pterostilbene derivatives Biomed. Res. Int. Article ID 320895

  15. (a) Arora S, Gonzalez A F and Solanki K 2013 Combretastatin A-4 and its Analogs in Cancer Therapy Int. J. Pharm. Sci. Rev. Res. 22 168

  16. (a) Tarade D, Pandey S and Mcnulty J 2017 Review of Cytotoxic CA4 Analogues that do not target microtubules: implications for CA4 development Mini-Rev. Med. Chem. 17 1507; (b) Hura N, Naaz A, Prassanawar S S, Guchhait S K and Panda D 2018 Drug-clinical agent molecular hybrid: synthesis of diaryl (trifluoromethyl) pyrazoles as tubulin targeting anticancer agents ACS Omega 3 1955

  17. Perez-Melero C, Maya A B S, Rey B, Pelaez R, Caballero E and Medarde M 2004 A new family of quinoline and quinoxaline analogues of combretastatins Bioorg. Med. Chem. Lett. 14 3771; (b) Tron G C, Pirali T, Sorba G, Pagliai F, Busacca S and Genazzani A A 2006 Medicinal chemistry of combretastatin A4: present and future directions J. Med. Chem. 49 3033

  18. Penthala N R, Janganati V, Bommagani S and Crooks P A 2014 Synthesis and evaluation of a series of quinolinyl trans-cyanostilbene analogs as anticancer agents Med. Chem. Commun. 5 886

    Article  CAS  Google Scholar 

  19. Zheng S, Zhong Q, Mottamal M, Zhang Q, Zhang C, LeMelle E, McFerrin H and Wang G 2014 Design, synthesis and biological evaluation of novel pyridine-bridged analogues of combretastatin-A4 as anticancer agents J. Med. Chem. 57 3369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Madadi N R, Penthala N R, Howk K, Ketkar A, Eoff R L, Borrelli M J and Crooks P A 2015 Synthesis and biological evaluation of novel 4, 5-disubstituted 2\(H\)-1, 2, 3-triazoles as cis-constrained analogues of combretastatin A-4 Eur. J. Med. Chem. 103 123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Demchuk D V, Samet A V, Chernysheva N B, Ushkarov V I, Stashina G A, Konyushkin L D, Raihstat M M, Firgang S I, Philchenkov A A, Zavelevich M P, Kuiava L M, Chekhun V F, Blokhin D Y, Kiselyov A S, Semenova M N and Semenov V V 2014 Synthesis and antiproliferative activity of conformationally restricted 1,2,3-triazole analogues of combretastatins in the sea urchin embryo model and against human cancer cell lines Bioorg. Med. Chem. 22 738

    Article  CAS  PubMed  Google Scholar 

  22. Zhang Q, Peng Y, Wang X I, Keenan S M, Arora S and Welsh W J 2007 Highly potent triazole-based tubulin polymerization inhibitors J. Med. Chem. 50 749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Duan Y T, Man R J, Tang D J, Yao Y F, Tao X X, Yu C, Liang X Y, Makawana J A, Zou M J, Wang Z C and Zhu H L 2016 Design, Synthesis and Antitumor Activity of Novel link-bridge and B-Ring Modified Combretastatin A-4 (CA-4) Analogues as Potent Antitubulin Agents Sci. Rep. 6 1

    Article  CAS  Google Scholar 

  24. Nguyen T T B, Lomberget T, Tran N C, Colomb E, Nachtergaele L, Thoret S, Dubois J, Guillaume J, Abdayem R, Haftek M and Barret R 2012 Synthesis and biological evaluation of novel heterocyclic derivatives of combretastatin A-4 Bioorg. Med. Chem. Lett. 22 7227

    Article  CAS  PubMed  Google Scholar 

  25. Soussi M A, Provot O, Bernadat G, Bignon J, Desravines D, Dubois J, Brion J D, Messaoudi S and Alami M 2015 IsoCombretaQuinazolines: potent cytotoxic agents with antitubulin activity Chem Med. Chem. 10 1392

    Article  CAS  PubMed  Google Scholar 

  26. Penthala N R, Sonar V N, Horn J, Leggas M, Yadlapallia J S K B and Crooks P A 2013 Synthesis and evaluation of a series of benzothiophene acrylonitrile analogs as anticancer agents Med. Chem. Commun. 4 1073

    Article  CAS  Google Scholar 

  27. Simoni D, Romagnoli R, Baruchello R, Rondanin R, Rizzi M, Pavani M G, Alloatti D, Giannini G, Marcellini M, Riccioni T, Castorina M, Guglielmi M B, Bucci F, Carminati P and Pisano C 2006 Novel combretastatin analogues endowed with antitumor activity J. Med. Chem. 49 3143

    Article  CAS  PubMed  Google Scholar 

  28. Greene L M, Wang S, O’boyle N M, Reid J E, Kelly P, Meegan M J 2013 Combretazet-3 a novel synthetic cis-stable combretastatin A-4-azetidinone hybrid with enhanced stability and therapeutic efficacy in colon cancer Oncol. Rep. 6 2451

    Article  CAS  PubMed  Google Scholar 

  29. Anurag, Pandeya S N, Singh U K and Sharma P P 2009 Synthesis and antiangiogenic activity of some novel combretastatin A-4 analogues Int. J. Pharma Clin. Res. 1 23

    Google Scholar 

  30. Guchhait S K, Sanghai N, Jain V, Preet R, Kandekar S, Das S, Trivedi N, Mohapatra P, Priyadarshani G, Kashyap M, Das D, Sathapathy S R, Siddharth S, Kundu C N and Bharatam P V 2014 Combretastatin A-4 inspired novel 2-aryl-3-arylamino-imidazo-pyridines/pyrazines as tubulin polymerization inhibitors, antimitotic and anticancer agents Med. Chem. Commun. 5 766

    Article  Google Scholar 

  31. Parihar S, Kumar A, Chaturvedi A K, Sachan N K, Luqman S, Changkija B, Manohar M, Prakash O, Chanda D, Khan F, Chanotiya C S, Shanker K, Dwivedi A, Konwar R and Negi A S 2013 Synthesis of combretastatin A4 analogues on steroidal framework and their anti-breast cancer activity J. Steroid Biochem. Mol. Bio. 137 332

    Article  CAS  Google Scholar 

  32. Kumar S, Mehndiratta S, Nepali K, Gupta M K, Koul S, Sharma P R, Saxena A K and Dhar K L 2013 Novel indole bearing combretastatin analogues as tubulin polymerization inhibitors Org. Med. Chem. Lett. 3 1

    Article  CAS  Google Scholar 

  33. Chaudhary V, Venghateri J B, Dhaked S H P, Bhoyar A S, Guchhait S K and Panda D 2016 Novel Combretastatin-2-aminoimidazole Analogues as Potent Tubulin Assembly Inhibitors: Exploration of Unique Pharmacophoric Impact of Bridging Skeleton and Aryl Moiety J. Med. Chem. 59 3439

    Article  CAS  PubMed  Google Scholar 

  34. Belleri M, Ribatti D, Nicoli S, Cotelli F, Forti L, Vannini V, Stivala L A and Presta M 2005 Antiangiogenic and Vascular-Targeting Activity of the Microtubule-Destabilizing trans-Resveratrol Derivative 3,5,4\(\prime \)-Trimethoxystilbene Mol. Pharmacol. 67 1451

  35. (a) Hu Y, Stumpfe D and Bajorath J 2017 Recent Advances in Scaffold Hopping J. Med. Chem. 60 1238; (b) Guchhait S K, Hura N, Sinha K and Panda D 2017 Pyridine C3-arylation of nicotinic acids accessible via a multicomponent reaction: an entry to all-substituted-3,4-diarylated pyridines RSC Adv. 7 8323

  36. (a) Morgan P, Van Der Graaf P H, Arrowsmith J, Feltner D E, Drummond K S, Wegner C D and Street S D A 2012 Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving phase II survival Drug Discov. Today 17 419; (b) van der Graaf P H and Benson N 2011 Systems pharmacology: bridging systems biology and pharmacokinetics-pharmacodynamics (PKPD) in drug discovery and development Pharm. Res. 28 1460

  37. Nayak S, Chakroborty S, Bhakta S, Panda P, Mohapatra S, Kumar S, Jena P K and Purohit C 2015 Design and Synthesis of (E)-4-(2-Phenyl-2H-chromen-3-yl)but-3-en-2-ones and Evaluation of their In Vitro Antimicrobial Activity Lett. Org. Chem. 12 352

    Article  CAS  Google Scholar 

  38. Zhang J, Lou C, Hu Z and Yan M 2009 Organocatalytic conjugate addition of nitroalkanes to 2H-chromene3-carbaldehydes: synthesis of highly functionalized chroman derivatives ARKIVOC 362

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Acknowledgements

SN and SRM are thankful to DST India (SR/FT/CS-139/2011 & SR/FT/CS-87/2012), UGC New Delhi (47-276/2013), UGC start-up-grant no. F.30-127/2015(BSR), CSIR New Delhi [02(0134)/13/EMR-II, 02(0218)/14/ EMR-II] for providing research grant. SMiLE project (IICT, Hyderabad) from CSIR, India is gratefully acknowledged.

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  1. Department of Chemistry, Ravenshaw University, Cuttack, 753 003, Odisha, India

    P Panda, S Nayak, S Bhakta & S Mohapatra

  2. Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, Telangana, India

    T R Murthy

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Correspondence to S Nayak.

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Panda, P., Nayak, S., Bhakta, S. et al. Design and synthesis of (Z/E)-2-phenyl/H-3-styryl-2H-chromene derivatives as antimicrotubule agents. J Chem Sci 130, 127 (2018). https://doi.org/10.1007/s12039-018-1520-6

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