Research Article
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Molecular Docking Studies and ADME Predictions on Synthesized Chalcone Compounds Targeting EGFR

Year 2023, , 167 - 175, 30.06.2023
https://doi.org/10.17350/HJSE19030000304

Abstract

In the present study, new chalcone derivatives (5a–5f) obtained from the condensation reaction of cuminaldehyde and acetophenone compounds containing different substituents were reported. Chemical characterization (1HNMR and 13CNMR analysis) and molecular docking studies of the synthesized compounds were performed against the epidermal growth factor receptor (EGFR) and reference drug (metachalcone). Erlotinib was used as the reference ligand. Compound 5 (-7.6 kcal mol-1), compound 6 (-7.38 kcal mol-1), and compound 7 (-7.44 kcal mol-1) were found to be the strongest inhibitors of EGFR when compared to Erlotinib (-7.0 kcal mol-1). In addition, an ADME estimation was made. It was determined that the synthesized compounds could be potent EGFR inhibitors compared to Erlotinib. Compounds 5-7 and the target protein showed a better binding affinity for EGFR than the reference compound (Erlotinib). The synthesized compounds can be potent inhibitors for EGFR-mutated cancers.

Supporting Institution

Kırşehir Ahi Evran University Scientific Research Projects (BAP)

Project Number

KMY.A4.21.001

References

  • 1. Kahriman N and Serdaroğlu V. Yeni Azakalkon-Şeker Hibrit Bileşiklerinin Sentezi. Gümüşhane Üniv. Fen Bil. Enst. Dergisi, 8(2) (2018) 442-454.
  • 2. Burmaoğlu S. Anti-Kanser Aktiviteye Sahip Bileşikler Olarak Flor- Sübstitüe Kalkonlar. Karaelmas Fen ve Müh. Dergisi, 7(2) (2017) 658-664.
  • 3. Arif R, Rana M, Yasmeen S, Khan A Md S, Abid M, and Khan M, Rahisuddin R. Facile Synthesis of Chalcone Derivatives as Antibacterial Agents: Synthesis, DNA Binding, Molecular Docking, DFT and Antioxidant Studies, Journal of Molecular Structure 1208 (2020): 127905.
  • 4. Lunardi F, Guzela M, Rodrigues A T, Correa R, Egermangrich I, Steindel M, Grisard E C, Assreuy J, Calixto, J B and Santos A R S. Tripanocidal and Leishmanicidal Properties of Substitution- Containing Chalcones. Antimic. Age. Chem., London, 47 (2003)1449-1451
  • 5. Mathew DGT, Parambi VS, Sivasankarapillai M S, Uddin J, Suresh G E, Mathew M, Marathakam J A, and Gupta S V. Perspective Design of Chalcones for the Management of CNS Disorders: A Mini-Review, CNS & Neurological Disorders Drug Targets 18, 6 (2019) 432–45.
  • 6. Hamed NA, Marzouk MI, Ismail MF, and Hekal MH. N’-(1- ([1,1’-Biphenyl]-4-yl)Ethylidene)-2-Cyanoacetohydrazide as Scaffold for the Synthesis of Diverse Heterocyclic Compounds as Prospective Antitumor and Antimicrobial Activities, Synthetic Communications 49, 21 (2019) 1–3029. 6.
  • 7. Ismail MF. and El-Sayed AA. Synthesis of Diverse Novel Compounds with Anticipated Antitumor Activities Starting with Biphenyl Chalcone, Journal of Heterocyclic Chemistry 57, 7 (2020) 2990–3001.
  • 8. Kaya S, Gokce H, Arslan T, and Alpaslan G. Synthesis, Spectroscopic Characterization, DFT Computations, Nonlinear Optical Profile and Molecular Docking Study of a Novel Chalcone Derivative, Journal of Molecular Structure 1202 (2020) 127270.
  • 9. Bonakdar APS, Vafaei F, Farokhpour M, Esfahani MHN, Massah AR. Synthesis and anticancer activity assay of novel chalconesulfonamide derivatives. Iran J Pharm Res, 16(2) (2017) 565–8.
  • 10. Zhuang C, ZhangW, Sheng C, Zhang W, Xing C, and Miao Z, Chalcone: A Privileged Structure in Medicinal Chemistry, Chem. Rev. 117, 12 (2017), 7762–7810
  • 11. Park S, Kim EH, Kim J, Kim SH, Kim I. Biological evaluation of indolizine-chalcone hybrids as new anticancer agents. Eur J Med Chem, 144 (2018) 435–43.
  • 12. Fogaça TB, Martins RM, Begnini KR, Carapina C, Ritter M, de Pereira CMP, Seixas FK, Collares T. Apoptotic effect of chalcone derivatives of 2-acetylthiophene in human breast cancer cells. Pharmacol Rep, 69 (2017)156–61
  • 13. Li PH, Jiang H, Zhang WJ, Li YL, Zhao MC, Zhou W, Zhang LY, Tang YD, Dong CZ, Huang ZS, Chen HX, Du ZY. Synthesis of carbazole derivatives containing chalcone analogs as nonintercalative topoisomerase II catalytic inhibitors and apoptosis inducers. Eur J Med Chem, 145 (2018) 498–510
  • 14. Yadav P, Lal K, Kumar A, Guru SK, Jaglan S, Bhushan S. Green synthesis and anticancer potential of chalcone linked-1,2,3- triazoles. Eur J Med Chem, 126 (2017) 944–53.
  • 15. Malose J. Mphahlele, Marole M. Maluleka, Nishal Parbhoo and Sibusiso T. Malindisa, Synthesis, Evaluation for Cytotoxicity and Molecular Docking Studies of Benzo[c]furan-Chalcones for Potential to Inhibit Tubulin Polymerization and/or EGFR-Tyrosine Kinase Phosphorylation Int. J. Mol. Sci. 19 (2018), 2552
  • 16. Han X, Peng B, Xiao B-B, Cao S-L, Yang C-R, Wang W-Z, Wang FC, Li HY, Yuan XL, Shi R, Liao J, Wang H, Li J, Xu X. Synthesis and evaluation of chalcone analogues containing a 4-oxoquinazolin-2- yl group as potential anti-tumor agents. Eur J Med Chem, 162 (2019) 586–601
  • 17. Madhavi S, Sreenivasulu R, Yazala JP, Raju RR. Synthesis of chalcone incorporated quinazoline derivatives as anticancer agents. Saudi Pharm J, 25(2017) 275–9
  • 18. Shankaraiah N, Siraj KP, Nekkanti S, Srinivasulu V, Sharma P, Senwar KR, Sathish M, Vishnuvardhan MVPS, Ramakrishna S, Jadala C, Nagesh N, Kamal A. DNA-binding affinity and anticancer activity of β-carboline-chalcone conjugates as potential DNA intercalators: molecular modelling and synthesis. Bioorg Chem, 59 (2015) 130–9.
  • 19. ÖZMEN ÖZGÜN D. (2021). Sülfonamit Artiği Taşiyan Yeni Pirazol Türevlerinin Sentezi Ve Sitotoksik Etkilerinin Araştirilmasi, Farmasötik Kimya Anabilim Dalı, Doktora Tezi-
  • 20. Synthesis of Novel Chalcone-Based Phenothiazine Derivatives as Antioxidant and Anticancer Agents, Nourah A. Al Zahrani, Reda M. El-Shishtawy, Mahmoud M. Elaasser, and Abdullah M. Asiri, Molecules. 25(19) (2020) 4566.
  • 21. Sinan Bilginer, Synthesis and Bioactivities of Benzoxazolone Derivative Chalcone Compounds Erzincan University Journal of Science and Technology 13(1) (2020) 334-347
  • 22. Karimov A, Orujova A, Taslimi P, Sadeghian N, Mammadov B, Karaman HS, Farzaliyev V, Sujayev E, Taş R, Alwasel S, Gulcin I. Novel functionally substituted esters based on sodium diethyldithiocarbamate derivatives: synthesis, characterization, biological activity and molecular docking studies, Bioorg. Chem., 99 (2020), 103762
  • 23. Mahmudov I, Demir Y, Sert Y, Abdullayev Y, Sujayev A, Saleh, Alwasel A, Gulcin I. Synthesis and inhibition profiles of N-benzyland N-allyl aniline derivatives against carbonic anhydrase and acetylcholinesterase – A molecular docking study, Arabian Journal of Chemistry, 15, 3 (2022) 10364
  • 24. Saini N, Grewal A S, Lather V, Gahlawat S K. Natural alkaloids targeting EGFR in non-small cell lung cancer: Molecular docking and ADMET predictions Chemico-Biological Interactions 358 (2022) 109901
  • 25. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep. 7 (2017) 42717.
  • 26. Tatar R. G, Kurşun Aktar B S. Bazı Kalkonların COVID-19 Tedavisine Yönelik SARS-CoV-2 Ana Proteaza Bağlanma Mekanizmasının Moleküler Kenetleme Yaklaşımı ile Aydınlatılması, Int. J. Adv. Eng. Pure Sci. 33(4) (2021) 660-669
Year 2023, , 167 - 175, 30.06.2023
https://doi.org/10.17350/HJSE19030000304

Abstract

Project Number

KMY.A4.21.001

References

  • 1. Kahriman N and Serdaroğlu V. Yeni Azakalkon-Şeker Hibrit Bileşiklerinin Sentezi. Gümüşhane Üniv. Fen Bil. Enst. Dergisi, 8(2) (2018) 442-454.
  • 2. Burmaoğlu S. Anti-Kanser Aktiviteye Sahip Bileşikler Olarak Flor- Sübstitüe Kalkonlar. Karaelmas Fen ve Müh. Dergisi, 7(2) (2017) 658-664.
  • 3. Arif R, Rana M, Yasmeen S, Khan A Md S, Abid M, and Khan M, Rahisuddin R. Facile Synthesis of Chalcone Derivatives as Antibacterial Agents: Synthesis, DNA Binding, Molecular Docking, DFT and Antioxidant Studies, Journal of Molecular Structure 1208 (2020): 127905.
  • 4. Lunardi F, Guzela M, Rodrigues A T, Correa R, Egermangrich I, Steindel M, Grisard E C, Assreuy J, Calixto, J B and Santos A R S. Tripanocidal and Leishmanicidal Properties of Substitution- Containing Chalcones. Antimic. Age. Chem., London, 47 (2003)1449-1451
  • 5. Mathew DGT, Parambi VS, Sivasankarapillai M S, Uddin J, Suresh G E, Mathew M, Marathakam J A, and Gupta S V. Perspective Design of Chalcones for the Management of CNS Disorders: A Mini-Review, CNS & Neurological Disorders Drug Targets 18, 6 (2019) 432–45.
  • 6. Hamed NA, Marzouk MI, Ismail MF, and Hekal MH. N’-(1- ([1,1’-Biphenyl]-4-yl)Ethylidene)-2-Cyanoacetohydrazide as Scaffold for the Synthesis of Diverse Heterocyclic Compounds as Prospective Antitumor and Antimicrobial Activities, Synthetic Communications 49, 21 (2019) 1–3029. 6.
  • 7. Ismail MF. and El-Sayed AA. Synthesis of Diverse Novel Compounds with Anticipated Antitumor Activities Starting with Biphenyl Chalcone, Journal of Heterocyclic Chemistry 57, 7 (2020) 2990–3001.
  • 8. Kaya S, Gokce H, Arslan T, and Alpaslan G. Synthesis, Spectroscopic Characterization, DFT Computations, Nonlinear Optical Profile and Molecular Docking Study of a Novel Chalcone Derivative, Journal of Molecular Structure 1202 (2020) 127270.
  • 9. Bonakdar APS, Vafaei F, Farokhpour M, Esfahani MHN, Massah AR. Synthesis and anticancer activity assay of novel chalconesulfonamide derivatives. Iran J Pharm Res, 16(2) (2017) 565–8.
  • 10. Zhuang C, ZhangW, Sheng C, Zhang W, Xing C, and Miao Z, Chalcone: A Privileged Structure in Medicinal Chemistry, Chem. Rev. 117, 12 (2017), 7762–7810
  • 11. Park S, Kim EH, Kim J, Kim SH, Kim I. Biological evaluation of indolizine-chalcone hybrids as new anticancer agents. Eur J Med Chem, 144 (2018) 435–43.
  • 12. Fogaça TB, Martins RM, Begnini KR, Carapina C, Ritter M, de Pereira CMP, Seixas FK, Collares T. Apoptotic effect of chalcone derivatives of 2-acetylthiophene in human breast cancer cells. Pharmacol Rep, 69 (2017)156–61
  • 13. Li PH, Jiang H, Zhang WJ, Li YL, Zhao MC, Zhou W, Zhang LY, Tang YD, Dong CZ, Huang ZS, Chen HX, Du ZY. Synthesis of carbazole derivatives containing chalcone analogs as nonintercalative topoisomerase II catalytic inhibitors and apoptosis inducers. Eur J Med Chem, 145 (2018) 498–510
  • 14. Yadav P, Lal K, Kumar A, Guru SK, Jaglan S, Bhushan S. Green synthesis and anticancer potential of chalcone linked-1,2,3- triazoles. Eur J Med Chem, 126 (2017) 944–53.
  • 15. Malose J. Mphahlele, Marole M. Maluleka, Nishal Parbhoo and Sibusiso T. Malindisa, Synthesis, Evaluation for Cytotoxicity and Molecular Docking Studies of Benzo[c]furan-Chalcones for Potential to Inhibit Tubulin Polymerization and/or EGFR-Tyrosine Kinase Phosphorylation Int. J. Mol. Sci. 19 (2018), 2552
  • 16. Han X, Peng B, Xiao B-B, Cao S-L, Yang C-R, Wang W-Z, Wang FC, Li HY, Yuan XL, Shi R, Liao J, Wang H, Li J, Xu X. Synthesis and evaluation of chalcone analogues containing a 4-oxoquinazolin-2- yl group as potential anti-tumor agents. Eur J Med Chem, 162 (2019) 586–601
  • 17. Madhavi S, Sreenivasulu R, Yazala JP, Raju RR. Synthesis of chalcone incorporated quinazoline derivatives as anticancer agents. Saudi Pharm J, 25(2017) 275–9
  • 18. Shankaraiah N, Siraj KP, Nekkanti S, Srinivasulu V, Sharma P, Senwar KR, Sathish M, Vishnuvardhan MVPS, Ramakrishna S, Jadala C, Nagesh N, Kamal A. DNA-binding affinity and anticancer activity of β-carboline-chalcone conjugates as potential DNA intercalators: molecular modelling and synthesis. Bioorg Chem, 59 (2015) 130–9.
  • 19. ÖZMEN ÖZGÜN D. (2021). Sülfonamit Artiği Taşiyan Yeni Pirazol Türevlerinin Sentezi Ve Sitotoksik Etkilerinin Araştirilmasi, Farmasötik Kimya Anabilim Dalı, Doktora Tezi-
  • 20. Synthesis of Novel Chalcone-Based Phenothiazine Derivatives as Antioxidant and Anticancer Agents, Nourah A. Al Zahrani, Reda M. El-Shishtawy, Mahmoud M. Elaasser, and Abdullah M. Asiri, Molecules. 25(19) (2020) 4566.
  • 21. Sinan Bilginer, Synthesis and Bioactivities of Benzoxazolone Derivative Chalcone Compounds Erzincan University Journal of Science and Technology 13(1) (2020) 334-347
  • 22. Karimov A, Orujova A, Taslimi P, Sadeghian N, Mammadov B, Karaman HS, Farzaliyev V, Sujayev E, Taş R, Alwasel S, Gulcin I. Novel functionally substituted esters based on sodium diethyldithiocarbamate derivatives: synthesis, characterization, biological activity and molecular docking studies, Bioorg. Chem., 99 (2020), 103762
  • 23. Mahmudov I, Demir Y, Sert Y, Abdullayev Y, Sujayev A, Saleh, Alwasel A, Gulcin I. Synthesis and inhibition profiles of N-benzyland N-allyl aniline derivatives against carbonic anhydrase and acetylcholinesterase – A molecular docking study, Arabian Journal of Chemistry, 15, 3 (2022) 10364
  • 24. Saini N, Grewal A S, Lather V, Gahlawat S K. Natural alkaloids targeting EGFR in non-small cell lung cancer: Molecular docking and ADMET predictions Chemico-Biological Interactions 358 (2022) 109901
  • 25. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep. 7 (2017) 42717.
  • 26. Tatar R. G, Kurşun Aktar B S. Bazı Kalkonların COVID-19 Tedavisine Yönelik SARS-CoV-2 Ana Proteaza Bağlanma Mekanizmasının Moleküler Kenetleme Yaklaşımı ile Aydınlatılması, Int. J. Adv. Eng. Pure Sci. 33(4) (2021) 660-669
There are 26 citations in total.

Details

Primary Language English
Subjects Food Technology
Journal Section Research Article
Authors

Özlem Gündoğdu 0000-0002-6943-9674

Project Number KMY.A4.21.001
Publication Date June 30, 2023
Submission Date March 2, 2023
Published in Issue Year 2023

Cite

Vancouver Gündoğdu Ö. Molecular Docking Studies and ADME Predictions on Synthesized Chalcone Compounds Targeting EGFR. Hittite J Sci Eng. 2023;10(2):167-75.

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