Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Synthesis, Biological Evaluation and Molecular Docking Study of Dihydropyrimidine Derivatives As Potential Anticancer Agents Publisher



Safari S1 ; Ghavimi R2 ; Razzaghiasl N1 ; Sepehri S1
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
  2. 2. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Journal of Heterocyclic Chemistry Published:2020


Abstract

A series of dihydropyrimidine analogues were prepared via one-pot Biginelli three-component condensation reaction and characterized by NMR, FT-IR, MS spectra, and element analysis. Subsequently, they were screened for in vitro anticancer effect. These analogues revealed good cytotoxic activity against three human cancer cell lines including MCF-7, HepG-2, and A549. Among these analogues, compounds 4d and 4h were the most potent against three cell lines. Cell viability assays indicated 4a and 4c had lower cytotoxicity. In vitro cytotoxicity study on all synthesized compounds demonstrated that introduction of electron withdrawing substituents on C4 position of phenyl ring of dihydropyrimidine contributed to the antiproliferative potency. Moreover, in silico molecular docking results stipulated a sign of good correlation between experimental activity and calculated binding affinity. It proved 4d and 4h as the strongest compounds. Binding modes of analogues proposed the involvement of hydrophobic interactions and hydrogen bonds with Eg5 active site. Structure activity relationship studies indicated that incorporating electron withdrawing substituents on C4 position of phenyl ring of dihydropyrimidine are important for this biological activity. © 2020 Wiley Periodicals, Inc.
Related Docs
View other Related Docs
1. Monastrol Derivatives: In Silico and in Vitro Cytotoxicity Assessments, Research in Pharmaceutical Sciences (2020)
2. Design, Synthesis and Molecular Docking Studies of Some Tetrahydropyrimidine Derivatives As Possible Fascin Inhibitors, Chemistry and Biodiversity (2019)
3. Hantzsch-Type Dihydropyridines and Biginelli-Type Tetrahydropyrimidines: A Review of Their Chemotherapeutic Activities, Journal of Pharmacy and Pharmaceutical Sciences (2015)
4. Antimicrobial Evaluation of Some Novel Derivatives of 3,4- Dihydropyrimidine-2(1H)-One, Research in Pharmaceutical Sciences (2012)
5. Design, Synthesis, and Anti-Hiv-1 Evaluation of a Novel Series of 1,2,3,4-Tetrahydropyrimidine-5-Carboxylic Acid Derivatives, Chemistry and Biodiversity (2018)
6. Synthesis, Characterization, Molecular Docking, Antimalarial, and Antiproliferative Activities of Benzyloxy-4-Oxopyridin Benzoate Derivatives, Research in Pharmaceutical Sciences (2022)
7. Synthesis and Cytotoxic Evaluation of Some Novel Diarylamide Possessing Quinoxalinedione Based on Sorafenib, Research in Pharmaceutical Sciences (2018)
8. Design, Synthesis, in Silico Studies, and Antiproliferative Evaluations of Novel Indolin-2-One Derivatives Containing 3-Hydroxy-4-Pyridinone Fragment, Bioorganic and Medicinal Chemistry Letters (2022)
Experts (# of related papers)
View all Related Experts
Afshin Fassihi (21)
Farshid Hassanzadeh (20)
Other Related Docs
9. Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel 4-[4-Arylpyridin-1(4H)-Yl]Benzoic Acid Derivatives As Anti-Hiv-1 Agents, Chemistry and Biodiversity (2017)
10. Synthesis and Antioxidant Evaluation of 4-(Furan-2-Yl)-6-Methyl-2- Thioxo-1,2,3,4-Tetrahydropyrimidine-5-Carboxylate Esters, Research in Pharmaceutical Sciences (2012)
11. Conformational Properties of Novel 1,2,3,4-Tetrahydropyrimidinone (Thione) Derivatives: A Dft Study, Journal of Reports in Pharmaceutical Sciences (2012)
12. Cytidine Derivatives As Inhibitors of Methyltransferase Enzyme, Eurasian Chemical Communications (2019)
13. Quantum Mechanical/Molecular Mechanical and Docking Study of the Novel Analogues Based on Hybridization of Common Pharmacophores As Potential Anti-Breast Cancer Agents, Research in Pharmaceutical Sciences (2017)
14. Synthesis, Characterization, Cytotoxic Screening, and Density Functional Theory Studies of New Derivatives of Quinazolin-4(3H)-One Schiff Bases, Research in Pharmaceutical Sciences (2017)
15. Design, Synthesis, and Bio-Evaluation of New Isoindoline-1,3-Dione Derivatives As Possible Inhibitors of Acetylcholinesterase, Research in Pharmaceutical Sciences (2021)
16. New 3-Hydroxypyridine-4-One Analogues: Their Synthesis, Antimicrobial Evaluation, Molecular Docking, and in Silico Adme Prediction, Medicinal Chemistry (2024)
17. Design, Synthesis, and Cytotoxicity Evaluation of Novel Indole-Acylhydrazone Derivatives of 4-Pyridinone As Potential Histone Deacetylase-2 Inhibitors, Research in Pharmaceutical Sciences (2022)
18. Anti-Cancer, Anti-Oxidant and Molecular Docking Studies of Thiosemicarbazone Indole-Based Derivatives, Research on Chemical Intermediates (2019)
19. Synthesis, Anti-Hiv-1 and Antiproliferative Evaluation of Novel 4-Nitroimidazole Derivatives Combined With 5-Hydroxy-4-Pyridinone Moiety, Journal of Molecular Structure (2020)
20. Design and Synthesis of Novel Cytotoxic Indole-Thiosemicarbazone Derivatives: Biological Evaluation and Docking Study, Chemistry and Biodiversity (2019)
21. Synthesis of Novel Conjugated Benzofuran-Triazine Derivatives: Antimicrobial and In-Silico Molecular Docking Studies, Heliyon (2023)
22. In Vitro Cytotoxicity Studies of Palladacyclic Complexes Containing the Symmetric Diphosphine Bridging Ligand. Studies of Their Interactions With Dna and Bsa, European Journal of Medicinal Chemistry (2014)
23. Synthesis, Calcium-Channel Blocking Activity, and Conformational Analysis of Some Novel 1,4-Dihydropyridines: Application of Pm3 and Dft Computational Methods, Medicinal Chemistry Research (2012)
24. Hydroxypyridinone Derivatives: Synthesis and Cytotoxic Evaluation, Journal of Reports in Pharmaceutical Sciences (2013)
25. Synthesis and Cytotoxic Evaluation of Some New 3-(2-(2-Phenylthiazol-4-Yl) Ethyl)-Quinazolin-4(3H) One Derivatives With Potential Anticancer Effects, Research in Pharmaceutical Sciences (2017)
26. Exploring the Interaction Between Epidermal Growth Factor Receptor Tyrosine Kinase and Some of the Synthesized Inhibitors Using Combination of In-Silico and In-Vitro Cytotoxicity Methods, Research in Pharmaceutical Sciences (2018)
27. Some Novel Hybrid Quinazoline-Based Heterocycles As Potent Cytotoxic Agents, Research in Pharmaceutical Sciences (2022)
28. Cytotoxic Effect of Pluronic F127-Poly (Methyl Vinyl Ether-Alt-Maleic Acid) Micelles Loaded With Doxorubicin on Mcf-7 Cells, Journal of Isfahan Medical School (2013)
29. Synthesis and Cytotoxic Evaluation of Two Novel Anthraquinone Derivatives, Farmaco (2004)
30. Dihydropyrimidine Derivatives As Mdm2 Inhibitors, Chemical Biology and Drug Design (2024)
31. Halogenated Derivatives of Cytidine: Structural Analysis and Binding Affnity, Journal of Theoretical and Computational Chemistry (2020)
32. Synthesis, Molecular Docking Studies, and Absorption, Distribution, Metabolism, and Excretion Prediction of Novel Sulfonamide Derivatives As Antibacterial Agents, Journal of the Chinese Chemical Society (2019)
33. An Integrated in Silico Screening Strategy for Identifying Promising Disruptors of P53-Mdm2 Interaction, Computational Biology and Chemistry (2019)
34. Synthesis and Cytotoxic Evaluation of Some Novel 3-[2-(2-Phenyl-Thiazol-4-Yl)-Ethyl] -3H-Pyrido [2,3-D]Pyrimidin-4-One Derivatives, Research in Pharmaceutical Sciences (2021)
35. Synthesis, Biological Activity Evaluation, Docking and Molecular Dynamics Studies of New Triazole-Tetrahydropyrimidinone(Thione) Hybrid Scaffolds As Urease Inhibitors, Chemistry and Biodiversity (2023)
36. Design of Novel Potential Aromatase Inhibitors Via Hybrid Pharmacophore Approach: Docking Improvement Using the Qm/Mm Method, RSC Advances (2015)
37. Biologically Active Heterocyclic Hybrids Based on Quinazolinone, Benzofuran and Imidazolium Moieties: Synthesis, Characterization, Cytotoxic and Antibacterial Evaluation, Chemistry and Biodiversity (2017)
38. Synthesis and Cytotoxic Activity Evaluation of Some New 1, 3, 4-Oxadiazole, 1, 3, 4-Thiadiazole and 1, 2, 4- Triazole Derivatives Attached to Phthalimide, Research in Pharmaceutical Sciences (2021)
39. Evaluation of the in Vitro Antiretroviral Potential of Some Biginelli-Type Pyrimidines, Acta Virologica (2012)
40. Qsar and Docking Studies of Some 1,2,3,4-Tetrahydropyrimidines: Evaluation of Gp41 As Possible Target for Anti-Hiv-1 Activity, Medicinal Chemistry Research (2015)
41. Synthesis and Cytotoxic Evaluation of Some New 4(3H)-Quinazolinones on Hela Cell Line, Research in Pharmaceutical Sciences (2012)
42. Synthesis and Antitubercular Activity of Novel 4-Substituted Imidazolyl-2,6-Dimethyl-N3,N5-Bisaryl-1,4-Dihydropyridine-3,5-Dicarboxamides, European Journal of Medicinal Chemistry (2009)
43. Novel N-Α-Amino Acid Spacer-Conjugated Phthalimide–Triazine Derivatives: Synthesis, Antimicrobial and Molecular Docking Studies, Amino Acids (2023)
44. Design, Synthesis, and Anticancer Activity of Phosphonic Acid Diphosphate Derivative of Adenine-Containing Butenolide and Its Water-Soluble Derivatives of Paclitaxel With High Antitumor Activity, Bioorganic and Medicinal Chemistry (2003)
45. The Art of Design in Azlactone-Benzoxazinone Chemistry, Docking Studies and in Vitro Cytotoxicity Evaluation, Australian Journal of Chemistry (2022)
46. Pyrimido[4,5-B]Indole Derivatives Bearing 1,2,4-Oxadiazole Moiety As Mdm2 Inhibitor Candidates in Cancer Treatment, Future Medicinal Chemistry (2023)
47. Biological Evaluation, Docking and Molecular Dynamic Simulation of Some Novel Diaryl Urea Derivatives Bearing Quinoxalindione Moiety, Research in Pharmaceutical Sciences (2017)
48. Synthesis, Qsar Modeling, and Molecular Docking Studies of 1,2,3-Triazole-Pyrazole Hybrids As Significant Anti-Cancer and Anti-Microbial Agents, Journal of Molecular Structure (2025)
49. Inhibitory Effect and Structure-Activity Relationship of Some Biginelli-Type Pyrimidines Against Hsv-1, Medicinal Chemistry Research (2013)
50. Cytidine Derivatives As Inhibitors of Methyltransferase Enzyme, Eurasian Chemical Communications (2020)