Synthesis, characterization, and anti-cancer activity of chalcone derivatives as-potent anaplastic lymphoma kinase inhibitors

Abstract

Chalcone derivatives (7a–k) have been synthesized and characterized by 1H-NMR, 13C-NMR, mass, and elemental analysis. The synthesized compounds 7a, 7d, and 7g have been examined and it is confirmed that the most promising cytotoxicity and also cell morphology analysis exhibited good apoptotic activity against lung cancer A549 cell. The free energy binding of compound 7d exhibits − 8.96 kcal/mol with five hydrogen bonding Asn1254, Arg1253, Asp1249, and Gly1123 amino acids of ALK receptors. The LUMO of the electron density present in α, β-double bond and influence the anticancer activity. The Mulliken atomic charges and MEPs are scrutinizing the ligand interaction with the amino acid binding of ALK receptors. UV-visible and photoluminescence spectra showed that the properties of chalcone derivatives have a significant effect on the visible absorption and emission maxima (531–535 nm) red shift in the emission spectra which also systematically investigated electrochemical in various solvents with increasing solvent polarity.

This is a preview of subscription content, access via your institution.

Fig. 1
Scheme 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Data availability

All data are included in this published article [supplementary information].

References

  1. 1.

    Yoon DW, Shin DW, Ho Cho J, Yang JH, Jeong SM, Han K, Park SH (2019). Lung Cancer 136:115–121

    PubMed  Article  PubMed Central  Google Scholar 

  2. 2.

    Siegel RL, Miller KD, Jemal A (2016). CA Cancer J Clin 66:7–30

    PubMed  Article  PubMed Central  Google Scholar 

  3. 3.

    Kwak EL, Bang YJ, Camid DR (2010). N Engl J Med 363:1693–1703

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Zhao X, Feng Z, Wang G, Pang H, Wang M (2018). Clin Lung Cancer 19:945–956

    Article  CAS  Google Scholar 

  5. 5.

    Mosse YP, Balis FM, Lim MS (2012). Am Soc Clin Oncolo 15:131–161

    Google Scholar 

  6. 6.

    Kinoshita K, Asoh K, Furuichi N, Ito T, Sousuke Hara HK, Ohwada J, Miyagi T, Kobayashi T, Takanashi K, Tsukaguchi T, Sakamoto H, Tsukuda T, Oikawa N (2012). Bioorg Med Chem 20:1271–1280

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    Rikova K, Guo A, Zeng Q (2007). Cel 131:1190–1203

    CAS  Article  Google Scholar 

  8. 8.

    Kang CH, Lee DH, Lee CO, Ha JD, Park CH, Hwang JY (2018). Biochem Biophys Res Commun 505:542–547

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  9. 9.

    Camidge DR, Doebele RC (2012). Nat Rev Clin Oncol 9:268–277

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. 10.

    Blackhall FH, Peters S, Kerr KM (2012). Ann Oncol 23:73–94

    Article  Google Scholar 

  11. 11.

    Bray F, Ren JS, Masuyer E, Ferlay J (2013). Int J Cancer 132:1133–1145

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  12. 12.

    Kwak EL, Bang YJ, Camidge DR, Shaw AT (2010). N Engl J Med 363:1693–1703

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    Wang WC, Shiao HY, Lee CC, Shu Fung K, Hsieh HP (2014). Med Chem Commun 5:1266–1279

    CAS  Article  Google Scholar 

  14. 14.

    Ou SH, Kwak EL, Tapp CS (2011). J Thorac Oncol 6:942–946

    PubMed  Article  Google Scholar 

  15. 15.

    Bergethon K, Shaw AT, Ou SH (2012). J Clin Oncol 30:863–870

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Cui JJ, Dube MT, Shen H, Nambu M, Kung P, Pairish M, Jia L, Meng J, Funk L, Botrous I, McTigue M, Grodsky N, Ryan K, Padrique E, Alton G, Timofeevski S, Yamazaki S, Li Q, Zou H, Christensen J, Mroczkowski B, Bender S, Kania S, Edwards MP (2011). J Med Chem 54:42–63

    Google Scholar 

  17. 17.

    Nielsen SF, Christensen SB, Cruciani G, Kharazmi A, Liljefors T (1998). J Med Chem 41:4819–4832

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  18. 18.

    Prakash G, Boopathy M, Selvam R, Kumar SJ, Subramanian K (2018). New J Chem 42:1037–1045

    CAS  Article  Google Scholar 

  19. 19.

    Lopez SN, Castelli MV, Zacchino SA, Dominguez JN, Lobo G, Jaime CC, Cortes CGJ, Ribas JC, Devia C, Ana MR, Ricardo DE (2001). Bioorg Med Chem 9:1999–2013

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  20. 20.

    Li R, Kenyon GL, Cohen FE, Chen X, Gong B, Dominguez JN, Davidson E, Kurzban G, Millar RE, Nuzum EO, Rosenthal PJ, Mckerrow JH (1995). J Med Chem 38:5031–5037

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  21. 21.

    Liu M, Wilairat P, Go ML (2001). J Med Chem 44:4443–4452

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  22. 22.

    Ko HH, Tsao LT, Yu KL, Liu CT, Wang JP, Lin CN (2003). Bioorg Med Chem 11:105–111

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  23. 23.

    Matsuda H, Morikawa T, Ando S, Iwao T, Masayuki Y (2003). Bioorg Med Chem 11:1995–2000

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  24. 24.

    Herencia F, Ferrandiz ML, Ubeda A, Dominguez JN, Charris JE, Lobo GM, Alcaraz M (1998). J Bioorg Med Chem Lett 8:1169–1174

    CAS  Article  Google Scholar 

  25. 25.

    Dias TA, Duarte CL, Lima CF, Proenca MF, Wilson CP (2013). Eur J Med Chem 65:500

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  26. 26.

    Wang Y, Xue S, Li R, Zheng Z, Yi H, Li Z (2018). Bioorg Med Chem 26:8–16

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  27. 27.

    Abonia R, Insuasty D, Castillo J, Insuasty B, Quiroga J, Nogueras M, Cobo J (2012). Eur J Med Chem 57:29–40

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  28. 28.

    Aziz MA, Park SE, Rahma DA, Gemmal EAR, Sayed MA, Kwon Y (2013). Eur J Med Chem 69:427–438

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  29. 29.

    Kim SY, Lee IS, Moon A (2013). Chem Biol Interact 203:565–572

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  30. 30.

    Murthy YLN, Suhasini KP, Pathania AS, Bhushan S, Sastry YN (2013). Eur J Med Chem 62:545–555

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  31. 31.

    Zhou XW, Ma HL, Zhang X, Jing SY, Miao JY, Zhao BX (2014). Eur J Med Chem 79:95–101

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  32. 32.

    Smith NM, Soh P, Asokananthan N, Norret M, Stewart GA, Raston CL (2009). New J Chem 33:1869–1873

    CAS  Article  Google Scholar 

  33. 33.

    Janet Sabina X, Karthikeyan J, Velmurugan G, Muthu Tamizh M, Nityananda Shettyd A (2017). New J Chem 41:4096–4109

    Article  Google Scholar 

  34. 34.

    Coskun D, Erkisa M, Ulukaya E, Coskun MF, Ari F (2017). Eur J Med Chem 136:212–222

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  35. 35.

    Sujin P, Kim EH, Jinwoo K, Kim SH, Ikyon K (2018). Eur J Med Chem 144:435–443

    Article  CAS  Google Scholar 

  36. 36.

    Adileh A, Rezvan E, Setareh M, Bakhshaiesh TO, Zahra ES, Keivan MA, Maliheh S, Saeed E, Alireza F (2018). Eur J Med Chem 155:483–491

    Article  CAS  Google Scholar 

  37. 37.

    Lakshmanan S, Govindaraj D, Ramalakshmi N, Arul Antony S (2017). J Mol Struct 1150:88–95

    CAS  Article  Google Scholar 

  38. 38.

    Lakshmanan S, Ramalakshmi N (2016). Synth Commun 46:2045–2052

    CAS  Article  Google Scholar 

  39. 39.

    Zhao K, Wang H, Sun H, Tian W, Yang S, Liu J, Peng J, Wang M (2017). New J Chem 41:14610–14617

    CAS  Article  Google Scholar 

  40. 40.

    Arias AC, MacKenzie JD, McCulloch I, Rivnay J, Salleo A (2010). Chem Rev 110:3–24

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  41. 41.

    Sun Y, Chen H, Caoa D, Liu Z, Chen H, Deng Y, Fang Q (2012). J Photochem Photobio A: Chem 244:65–70

    CAS  Article  Google Scholar 

  42. 42.

    Ghate NB, Hazra B, Sarkar R, Mandal N (2014). Cytotechnology 66:209–218

    PubMed  Article  PubMed Central  Google Scholar 

  43. 43.

    Lee YR, Yu DS, Liang YC, Huang KF, Chou SJ, Chen TC, Lee CC, Chen LC, Chiou SH, Huang HS, In vitro cytotoxicity assay

  44. 44.

    Denizot F, Lang R (1986). J Immunol Methods 89:271–277

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  45. 45.

    Chen CL, Chang DM, Chen TC, Lee CC, Hsieh HH (2013). Eur J Med Chem 60:29–41

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  46. 46.

    Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009). J Comput Chem 16:2785–2791

    Article  CAS  Google Scholar 

  47. 47.

    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery Jr JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2010) Gaussian 09. Revision B.01. Gaussian, Inc, Wallingford

  48. 48.

    Keith T, Millam J (2009) Gauss view 5. Semichem Inc Shawnee Mission KS

  49. 49.

    Sebastian SHR, Alshaikh MAA, Emam AAE, Panicker CY, Zitko J, Dolezal M, Alsenoy CV (2016). J Mol Struct 1119:188–199

    CAS  Article  Google Scholar 

  50. 50.

    Ali A, Asif M, Alam P, Alam MJ, Sherwani MA, Khan RH, Ahmad S (2017) Shamsuzzaman. Bioorg Chem 73:83–99

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  51. 51.

    Bavadi M, Niknam K, Shahraki O (2017). J Mole Struc 1146:242–253

    CAS  Article  Google Scholar 

  52. 52.

    Parr RJ, Szentpaly LV, Liu S (1999). J Am Chem Soc 121:1922–1924

    CAS  Article  Google Scholar 

  53. 53.

    Hosomi A, Fujita M, Tomioka A, Kaji H, Suzuki T (2016). Biochem J 19:3001–3012

    Article  CAS  Google Scholar 

  54. 54.

    Katsori AM, Litina DH (2009). Curr Med Chem 16:1062–1081

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  55. 55.

    Batovski DI, Parushev SP (2010). Int J Curr Chem 1:217–236

    Google Scholar 

  56. 56.

    Boumendjel A, Boccard J, Carrupt PA, Nicolle E, Blanc M, Geze A, Choisnard L, Wouessidjewe D, Matera EL, Dumontet C (2008). J Med Chem 51:2307–2310

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  57. 57.

    Chang Y, Li Y, Ye N, Guo X, Li Z, Sun G, Sun Y (2016). Apoptosis 21:977

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  58. 58.

    Anandkumar D, Ganesan S, Rajakumar P, Maruthamuthu P (2017). New J Chem 41:11238–11249

    CAS  Article  Google Scholar 

  59. 59.

    Bodapati JB, Icil H (2011). Photochem Photobiol Sci 10:1283–1293

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Amiralaei S, Uzun D, Icil H (2008). Photochem Photobiol Sci 7:936–947

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  61. 61.

    Mostafanejad SM, Bodapati JB, Ozkar S, Icil H, (2018). Optic Mate 82: 30–38

Download references

Author information

Affiliations

Authors

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by [Sivalingam Lakshmanan], [Dharman Govindaraj], [K. Mahalakshmi], [K. Thirumurugan], [N. Ramalakshmi], and [S. Arul Antony]. The first draft of the manuscript was written by [Sivalingam Lakshmanan] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sivalingam Lakshmanan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 1958 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lakshmanan, S., Govindaraj, D., Mahalakshmi, K. et al. Synthesis, characterization, and anti-cancer activity of chalcone derivatives as-potent anaplastic lymphoma kinase inhibitors. Struct Chem (2021). https://doi.org/10.1007/s11224-020-01707-5

Download citation

Keywords

  • Photochemical
  • Electrochemical
  • Chalcone
  • Molecular docking
  • DFT
  • Anticancer activity
  • Apoptosis