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image of Targeting Breast Cancer: Novel Dihydropyrimidinones As Potent Eg5 
Inhibitors

Abstract

Introduction

Breast cancer remains a formidable health concern for women, necessitating the development of potent anticancer agents with improved safety profiles. Dihydropyrimidinones (DHPM), pyrazole, and benzofuran scaffolds have emerged as promising targets due to their diverse pharmacological profiles. In this study, we employed a scaffold hopping approach to design a novel DHPM-Pyrazole-Benzofuran core. A series of compounds were synthesized using the Biginelli protocol, and their characterization was performed using various techniques such as FTIR, 1H NMR, and Mass spectroscopy.

Methods

Molecular docking studies against kinesin spindle protein Eg5 (1Q0B) performed to find superior binding interactions compared to the prototype Eg5 inhibitor Monastrol. Anti breast cancer potential of these compounds was screened against the breast adrenocarcinoma MCF-7 cell line using an SRB assay.

Results

Compound showed good growth inhibitory activity (GI=24.08μM) compared to Monastrol (GI=32μM) employed as a positive control. Moreover, Compound exhibited strong interactions with amino acids GLU-116 and ARG-119 with Eg5 protein 1Q0B.

Conclusion

Compound fits well at the allosteric site of Eg5 protein 1QOB. Compound emerged as the most cytotoxic, displaying significant and impressive growth inhibitory activity (GI=24.08μM).

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2025-01-08

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References

  1. Hanahan D. Weinberg R.A. The hallmarks of cancer. Cell 2000 100 1 57 70 10.1016/S0092‑8674(00)81683‑9 10647931
    [Google Scholar]
  2. Hanahan D. Weinberg R.A. Hallmarks of cancer: The next generation. Cell 2011 114 5 646 674
    [Google Scholar]
  3. Vogelstein B. Kinzler K.W. Cancer genes and the pathways they control. Nat. Med. 2004 10 8 789 799
    [Google Scholar]
  4. Giaquinto A.N. Sung H. Miller K.D. Kramer J.L. Newman L.A. Minihan A. Jemal A. Siegel R.L. Breast cancer statistics. CA Cancer J. Clin. 2022 72 6 524 541 10.3322/caac.21754 36190501
    [Google Scholar]
  5. Deo S.V.S. Sharma J. Kumar S. GLOBOCAN 2020 report on global cancer burden: challenges and opportunities for surgical oncologists. Ann. Surg. Oncol. 2022 29 11 6497 6500 10.1245/s10434‑022‑12151‑6 35838905
    [Google Scholar]
  6. GLOBOCAN U. New global cancer data. UICC 2020 27 2022
    [Google Scholar]
  7. DeSantis C.E. Ma J. Gaudet M.M. Newman L.A. Miller K.D. Goding Sauer A. Jemal A. Siegel R.L. Breast cancer statistics, 2019. CA Cancer J. Clin. 2019 69 6 438 451 10.3322/caac.21583 31577379
    [Google Scholar]
  8. Sung H. Ferlay J. Siegel R.L. Laversanne M. Soerjomataram I. Jemal A. Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021 71 3 209 249 10.3322/caac.21660 33538338
    [Google Scholar]
  9. Bray F. Laversanne M. Sung H. Ferlay J. Siegel R.L. Soerjomataram I. Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2024 74 3 229 263 10.3322/caac.21834 38572751
    [Google Scholar]
  10. Hassan M. Watari H. AbuAlmaaty A. Ohba Y. Sakuragi N. Apoptosis and molecular targeting therapy in cancer. BioMed Res. Int. 2014 2014 28 1 23 10.1155/2014/150845 25013758
    [Google Scholar]
  11. Guido B.C. Ramos L.M. Nolasco D.O. Nobrega C.C. Andrade B.Y.G. Pic-Taylor A. Neto B.A.D. Corrêa J.R. Impact of kinesin Eg5 inhibition by 3,4-dihydropyrimidin-2(1H)-one derivatives on various breast cancer cell features. BMC Cancer 2015 15 1 283 10.1186/s12885‑015‑1274‑1 25885813
    [Google Scholar]
  12. Garcia-Saez I. Skoufias D.A. Eg5 targeting agents: From new anti-mitotic based inhibitor discovery to cancer therapy and resistance. Biochem. Pharmacol. 2021 184 114364 10.1016/j.bcp.2020.114364 33310050
    [Google Scholar]
  13. Wood K. Cornwell W.D. Jackson J.R. Past and future of the mitotic spindle as an oncology target. Curr. Opin. Pharmacol. 2001 1 4 370 377 10.1016/S1471‑4892(01)00064‑9 11710735
    [Google Scholar]
  14. Mayer T.U. Kapoor T.M. Haggarty S.J. King R.W. Schreiber S.L. Mitchison T.J. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen Science 1999 286 5441 971 10.1126/science.286.5441.971
    [Google Scholar]
  15. Jin Q. Huang F. Wang X. Zhu H. Xian Y. Li J. Zhang S. Ni Q. High Eg5 expression predicts poor prognosis in breast cancer. Oncotarget 2017 8 37 62208 62216 10.18632/oncotarget.19215 28977938
    [Google Scholar]
  16. Ferhat L. Cook C. Chauviere M. Harper M. Kress M. Lyons G.E. Baas P.W. Expression of the mitotic motor protein Eg5 in postmitotic neurons: Implications for neuronal development. J. Neurosci. 1998 18 19 7822 7839 10.1523/JNEUROSCI.18‑19‑07822.1998
    [Google Scholar]
  17. Carter B.Z. Mak D.H. Shi Y. Schober W.D. Wang R.Y. Konopleva M. Koller E. Dean N.M. Andreeff M. Regulation and targeting of Eg5, a mitotic motor protein in blast crisis CML: Overcoming imatinib resistance. Cell Cycle 2006 5 19 2223 2229 10.4161/cc.5.19.3255
    [Google Scholar]
  18. Castillo A. Morse H.C. III Godfrey V.L. Naeem R. Justice M.J. Overexpression of Eg5 causes genomic instability and tumor formation in mice. Canc. Res. 2007 67 21 10138 10147 10.1158/0008‑5472.CAN‑07‑0326
    [Google Scholar]
  19. Liu M. Yu H. Huo L. Liu J. Li M. Zhou J. Validating the mitotic kinesin Eg5 as a therapeutic target in pancreatic cancer cells and tumor xenografts using a specific inhibitor. Biochem. Pharmacol. 2008 76 2 169 178 10.1016/j.bcp.2008.04.018 18539263
    [Google Scholar]
  20. Joshi H.C. Microtubule dynamics in living cells. Curr. Opin. Cell Biol. 1998 10 1 35 44 10.1016/S0955‑0674(98)80084‑7
    [Google Scholar]
  21. Attri P. Bhatia R. Gaur J. Arora B. Gupta A. Kumar N. Choi E.H. Triethylammonium acetate ionic liquid assisted one-pot synthesis of dihydropyrimidinones and evaluation of their antioxidant and antibacterial activities. Arab. J. Chem. 2017 10 2 206 214 10.1016/j.arabjc.2014.05.007
    [Google Scholar]
  22. de Vasconcelos A. Oliveira P.S. Ritter M. Freitag R.A. Romano R.L. Quina F.H. Pizzuti L. Pereira C.M.P. Stefanello F.M. Barschak A.G. Antioxidant capacity and environmentally friendly synthesis of dihydropyrimidin‐(2 H )‐ones promoted by naturally occurring organic acids. J. Biochem. Mol. Toxicol. 2012 26 4 155 161 10.1002/jbt.20424 22447704
    [Google Scholar]
  23. Gangwar N. Kasana V.K. 3,4-Dihydropyrimidin-2(1H)-one derivatives: Organocatalysed microwave assisted synthesis and evaluation of their antioxidant activity. Med. Chem. Res. 2012 21 12 4506 4511 10.1007/s00044‑012‑9987‑z
    [Google Scholar]
  24. Huang X. Tu Z. Jiang Y. Xiao H. Zhang Q. Wang H. Dynamic high pressure microfluidization-assisted extraction and antioxidant activities of lentinan. Int. J. Biol. Macromol. 2012 51 5 926 932 10.1016/j.ijbiomac.2012.07.018 22829052
    [Google Scholar]
  25. Barbosa F.A.R. Canto R.F.S. Saba S. Rafique J. Braga A.L. Synthesis and evaluation of dihydropyrimidinone-derived selenoesters as multi-targeted directed compounds against Alzheimer’s disease. Bioorg. Med. Chem. 2016 24 22 5762 5770 10.1016/j.bmc.2016.09.031 27681239
    [Google Scholar]
  26. Stefani H.A. Oliveira C.B. Almeida R.B. Pereira C.M.P. Braga R.C. Cella R. Borges V.C. Savegnago L. Nogueira C.W. Dihydropyrimidin-(2H)-ones obtained by ultrasound irradiation: A new class of potential antioxidant agents. Eur. J. Med. Chem. 2006 41 4 513 518 10.1016/j.ejmech.2006.01.007 16516351
    [Google Scholar]
  27. Matthews J.M. Liotta F. Hageman W. Rivero R.A. Westover L. Yang M. Xu J. Demarest K. Discovery of a dihydropyrimidine series of molecules that selectively mimic the biological actions of calcitonin. Bioorg. Med. Chem. Lett. 2004 14 5 1155 1159 10.1016/j.bmcl.2003.12.071 14980655
    [Google Scholar]
  28. China Raju B. Nageswara Rao R. Suman P. Yogeeswari P. Sriram D. Shaik T.B. Kalivendi S.V. Synthesis, structure–activity relationship of novel substituted 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylates as potential anti-mycobacterial and anticancer agents. Bioorg. Med. Chem. Lett. 2011 21 10 2855 2859 10.1016/j.bmcl.2011.03.079 21507635
    [Google Scholar]
  29. Prasad T. Mahapatra A. Sharma T. Sahoo C.R. Padhy R.N. Dihydropyrimidinones as potent anticancer agents: Insight into the structure–activity relationship. Arch. Pharm. (Weinheim) 2023 356 6 2200664 10.1002/ardp.202200664 36942985
    [Google Scholar]
  30. Dowarah J. Patel D. Marak B.N. Yadav U.C.S. Shah P.K. Shukla P.K. Singh V.P. Green synthesis, structural analysis and anticancer activity of dihydropyrimidinone derivatives. RSC Advances 2021 11 57 35737 35753 10.1039/D1RA03969E 35492774
    [Google Scholar]
  31. Zhu L. Cheng P. Lei N. Yao J. Sheng C. Zhuang C. Guo W. Liu W. Zhang Y. Dong G. Wang S. Miao Z. Zhang W. Synthesis and biological evaluation of novel homocamptothecins conjugating with dihydropyrimidine derivatives as potent topoisomerase I inhibitors. Arch. Pharm. (Weinheim) 2011 344 11 726 734 10.1002/ardp.201000402 21956522
    [Google Scholar]
  32. S T. Mahendran H.P. Bhattacharjee R.R. Jeyaraj S. Mohanta K. Assessment of dihydropyrimidinone-based nanocomposites as multifunctional anti-cancer drug. Mater. Adv. 2021 2 10 3385 3393 10.1039/D1MA00017A
    [Google Scholar]
  33. Benazir Ali L. Subramani A. Jamal Ahamed V.S. Patel P.V. Shabeer T.K. Tamizhdurai P. Syed A. Al-Shwaiman H. Sasikumar P. In silico investigation and biological evaluation viz antimicrobial, genotoxic, and anticancer potentials of new dihydropyrimidinones (DHPMs) synthesized by Biginelli reaction. J. Mol. Struct. 2024 1316 138758 10.1016/j.molstruc.2024.138758
    [Google Scholar]
  34. Adigun R.A. Malan F.P. Balogun M.O. October N. Design, synthesis, and in silico-in vitro antimalarial evaluation of 1,2,3-triazole-linked dihydropyrimidinone quinoline hybrids. Struct. Chem. 2023 34 6 2065 2082 10.1007/s11224‑023‑02142‑y
    [Google Scholar]
  35. Rogerio K.R. Graebin C.S. Pinto Domingues L.H. Oliveira L.S. de Souza Fernandes da Silva V. Daniel-Ribeiro C.T. Carvalho L.J.M. Boechat N. Novel Quinolinyl-pyrrolo[3,4-d]pyrimidine-2,5-dione derivatives against chloroquine-resistant Plasmodium falciparum. Curr. Top. Med. Chem. 2020 20 2 99 110 10.2174/1568026619666191019100711 31648638
    [Google Scholar]
  36. Parth K. Kaur H. Persoons L. Andrei G. Singh K. Quinoline‐Dihydropyrimidin‐2(1 H )‐one Hybrids: Synthesis, biological activity, and mechanistic studies. ChemMedChem 2022 17 8 e202200031 10.1002/cmdc.202200031 35174629
    [Google Scholar]
  37. Rogerio K.R. Carvalho L.J.M. Domingues L.H.P. Neves B.J. Moreira Filho J.T. Castro R.N. Bianco Júnior C. Daniel-Ribeiro C.T. Andrade C.H. Graebin C.S. Synthesis and molecular modelling studies of pyrimidinones and pyrrolo[3,4-d]-pyrimidinodiones as new antiplasmodial compounds. Mem. Inst. Oswaldo Cruz 2018 113 8 e170452 10.1590/0074‑02760170452 29924131
    [Google Scholar]
  38. Radini I. Elsheikh T. El-Telbani E. Khidre R. New potential antimalarial agents: Design, synthesis and biological evaluation of some novel quinoline derivatives as antimalarial agents. Molecules 2016 21 7 909 10.3390/molecules21070909 27428939
    [Google Scholar]
  39. Ramachandran V. Arumugasamy K. Singh S.K. Edayadulla N. Ramesh P. Kamaraj S.K. Synthesis, antibacterial studies, and molecular modeling studies of 3,4-dihydropyrimidinone compounds. J. Chem. Biol. 2016 9 1 31 40 10.1007/s12154‑015‑0142‑4 26855679
    [Google Scholar]
  40. Santos S.J. Rossatto F.C.P. Jardim N.S. Ávila D.S. Ligabue-Braun R. Fontoura L.A.M. Zimmer K.R. Russowsky D. Chromene-dihydropyrimidinone and xanthene-dihydropyrimidinone hybrids: Design, synthesis, and antibacterial and antibiofilm activities. New J. Chem. 2023 47 16 7500 7520 10.1039/D2NJ05211C
    [Google Scholar]
  41. Venugopala K. Rao D. Bhandary S. Pillay M. Chopra D. Aldhubiab B. Attimarad M. Alwassil O. Harsha S. Mlisana K. Design, synthesis, and characterization of (1-(4-aryl)-1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates against Mycobacterium tuberculosis. Drug Des. Devel. Ther. 2016 10 2681 2690 10.2147/DDDT.S109760 27601885
    [Google Scholar]
  42. El-Shoukrofy M.S. Atta A. Fahmy S. Sriram D. Mahran M.A. Labouta I.M. New tetrahydropyrimidine-1,2,3-triazole clubbed compounds: Antitubercular activity and Thymidine Monophosphate Kinase (TMPKmt) inhibition. Bioorg. Chem. 2023 131 106312 10.1016/j.bioorg.2022.106312 36528922
    [Google Scholar]
  43. Priya N. Singh P. Bhatia S. Medhi B. Prasad A.K. Parmar V.S. Raj H.G. Characterization of a unique dihydropyrimidinone, ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate, as an effective antithrombotic agent in a rat experimental model. J. Pharm. Pharmacol. 2011 63 9 1175 1185 10.1111/j.2042‑7158.2011.01316.x 21827490
    [Google Scholar]
  44. Chikhale R.V. Bhole R.P. Patil P.A. Khedekar P.B. Bhusari K.P. Synthesis and antimicrobial activity of some ethyl [6-methyl-2-methoxy-3-(substituted phenylethanone)-4-(substituted phenyl)]-1, 2, 3, 4-tetrahydropyrimidine-5-carboxylates. Pharma Chem. 2009 1 1 247 257
    [Google Scholar]
  45. Almansour I. Ashraf Ali A. Ali M. Chee Wei A. Keng Yoon Y. Ismail R. Osman H. Antimycobacterial agents: synthesis and biological evaluation of novel 4-(substituted-phenyl)-6-methyl-2-oxo-N-(pyridin-2-yl)-1, 2, 3, 4-tetrahydropyrimidine-5-carboxamide derivatives by using one-pot multicomponent method. Lett. Drug Des. Discov. 2012 9 10 953 957 10.2174/1570180811209050953
    [Google Scholar]
  46. Khasimbi S. Ali F. Manda K. Sharma A. Chauhan G. Wakode S. Dihydropyrimidinones scaffold as a promising nucleus for synthetic profile and various therapeutic targets: A Review. Curr. Org. Synth. 2021 18 3 270 293 10.2174/1570179417666201207215710 33290199
    [Google Scholar]
  47. Morita I. Kunimoto K. Tsuda M. Tada S. I. Kise M. Kimura K. Synthesis and antihypertensive activities of 1, 4-dihydropyridine-5-phosphonate derivatives. II. Chem. Pharm. Bull. 35 10 4144 4154
    [Google Scholar]
  48. Bansal R. Narang G. Calle C. Carron R. Pemberton K. Harvey A.L. Synthesis of 4‐(Carbonyloxyphenyl)‐1,4‐Dihydropyridines as Potential Antihypertensive Agents. Drug Dev. Res. 2013 74 1 50 61 10.1002/ddr.21056
    [Google Scholar]
  49. Alam O. Khan S.A. Siddiqui N. Ahsan W. Verma S.P. Gilani S.J. Antihypertensive activity of newer 1,4-dihydro-5-pyrimidine carboxamides: Synthesis and pharmacological evaluation. Eur. J. Med. Chem. 2010 45 11 5113 5119 10.1016/j.ejmech.2010.08.022 20813434
    [Google Scholar]
  50. Sakoda R. Kamikawaji Y. Seto K. Synthesis of 1, 4-dihydropyridine-5-phosphonates and their calcium-antagonistic and antihypertensive activities: Novel calcium-autagonist 2-[benzy (phenyl) amino] ethyl 5-(5, 5-dimethyl-2-oxo-1, 3, 2-dioxaphosphorinan-2-yl)-1, 4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3-phrixinecarboaylate hydrochloride ethanol (NZ-105) and its crystal structure. Chem. Pharm. Bull. (Tokyo) 1992 40 9 2362 2369 10.1248/cpb.40.2362 1446356
    [Google Scholar]
  51. Kim J. Park C. Ok T. So W. Jo M. Seo M. Kim Y. Sohn J.H. Park Y. Ju M.K. Kim J. Han S.J. Kim T.H. Cechetto J. Nam J. Sommer P. No Z. Discovery of 3,4-dihydropyrimidin-2(1H)-ones with inhibitory activity against HIV-1 replication. Bioorg. Med. Chem. Lett. 2012 22 5 2119 2124 10.1016/j.bmcl.2011.12.090 22305583
    [Google Scholar]
  52. Kim J. Kwon J. Lee D. Jo S. Park D.S. Choi J. Park E. Hwang J.Y. Ko Y. Choi I. Ju M.K. Serendipitous discovery of 2-((phenylsulfonyl) methyl)-thieno [3, 2-d] pyrimidine derivatives as novel HIV-1 replication inhibitors. Bioorg. Med. Chem. Lett 2014 24 23 5473 5477
    [Google Scholar]
  53. Pagano N. Teriete P. Mattmann M.E. Yang L. Snyder B.A. Cai Z. Heil M.L. Cosford N.D.P. An integrated chemical biology approach reveals the mechanism of action of HIV replication inhibitors. Bioorg. Med. Chem. 2017 25 23 6248 6265 10.1016/j.bmc.2017.03.061 28442262
    [Google Scholar]
  54. Khan M.M. Saigal Khan S. Shareef S. Danish M. Organocatalyzed synthesis and antifungal activity of fully substituted 1,4‐Dihydropyridines. ChemistrySelect 2018 3 24 6830 6835 10.1002/slct.201800709
    [Google Scholar]
  55. Appna N.R. Nagiri R.K. Korupolu R.B. Kanugala S. Chityal G.K. Thipparapu G. Banda N. Design and synthesis of novel 4-hydrazone functionalized/1,2,4-triazole fused pyrido[2,3-d]pyrimidine derivatives, their evaluation for antifungal activity and docking studies. Med. Chem. Res. 2019 28 9 1509 1528 10.1007/s00044‑019‑02390‑w
    [Google Scholar]
  56. Zhang J. Peng J.F. Wang T. Wang P. Zhang Z.T. Synthesis, crystal structure, characterization and antifungal activity of pyrazolo[1,5-a]pyrimidines derivatives. J. Mol. Struct. 2016 1120 228 233 10.1016/j.molstruc.2016.05.026
    [Google Scholar]
  57. Castro Jara M. Silva A.C.A. Ritter M. da Silva A.F. Gonçalves C.L. dos Santos P.R. Borja L.S. de Pereira C.M.P. da Silva Nascente P. Dihydropyrimidinones against multiresistant bacteria. Front. Microbiol. 2022 13 743213 10.3389/fmicb.2022.743213 35369453
    [Google Scholar]
  58. Selvinthanuja C. Kiruthiga N. Prabha T. Sivakumar T. Subramanian N. Synthesis, characterization, molecular docking and antimicrobial evaluation of azo coupled-3, 4-dihydropyrimidine-2 (1h)-one derivatives. IJPRAS 2021 10 6 3992 3999
    [Google Scholar]
  59. Jackson J.R. Patrick D.R. Dar M.M. Huang P.S. Targeted anti-mitotic therapies: Can we improve on tubulin agents? Nat. Rev. Cancer 2007 7 2 107 117 10.1038/nrc2049 17251917
    [Google Scholar]
  60. Yadlapalli R. K. Chourasia O.P. Kiranmayi V. Manjula S. Sridhar R. Synthesis and in vitro anticancer and antitubercular activity of diarylpyrazole ligated dihydropyrimidines possessing lipophilic carbamoyl group. Bioorg. Med. Chem. Lett 2012 22 8 2708 2711
    [Google Scholar]
  61. Nikam D. Jain A. Advances in the discovery of DHPMs as Eg5 inhibitors for the management of breast cancer and glioblastoma: A review. Results Chem. 2023 5 5 100718 10.1016/j.rechem.2022.100718
    [Google Scholar]
  62. Russowsky D. Canto R.F. Sanches S.A. D’Oca M.G. de Fátima A. Pilli R.A. Kohn L.K. Anto^nio M.A. de Carvalho J.E. Synthesis and differential antiproliferative activity of Biginelli compounds against cancer cell lines: Monastrol, oxo-monastrol, and oxygenated analogs. Bioorg. Chem. 2006 34 4 173 182 10.1016/j.bioorg.2006.04.003
    [Google Scholar]
  63. Soumyanarayanan U. Bhat V.G. Kar S.S. Mathew J.A. Monastrol mimic Biginelli dihydropyrimidinone derivatives: Synthesis, cytotoxicity screening against HepG2 and HeLa cell lines and molecular modeling study. Org. Med. Chem. Lett. 2012 2 1 23 10.1186/2191‑2858‑2‑23 22691177
    [Google Scholar]
  64. El-Hamamsy M.H. Sharafeldin N.A. El-Moselhy T.F. Tawfik H.O. Design, synthesis, and molecular docking study of new monastrol analogues as kinesin spindle protein inhibitors. Arch. Pharm. (Weinheim) 2020 353 8 2000060 10.1002/ardp.202000060 32452567
    [Google Scholar]
  65. Kumar N. Sreenivasa S. Prashant A. Kumar V. Holla B.S. Chandramohan V. Vishwantha P. Yadav A.K. N’-((3-(substituted phenyl)-1-phenyl-1H-Pyrazol-4-yl)methylene)-(substituted) benzhydrazide: Synthesis, characterization and pharmacological evaluation. Chem. Data Collect. 2021 1 32 10066
    [Google Scholar]
  66. Napiórkowska M. Cieślak M. Kaźmierczak-Barańska J. Królewska-Golińska K. Nawrot B. Synthesis of new derivatives of benzofuran as potential anticancer agents. Molecules 2019 24 8 1529 10.3390/molecules24081529
    [Google Scholar]
  67. Azimi F. Azizian H. Najafi M. Khodarahmi G. Saghaei L. Hassanzadeh M. Ghasemi J.B. Faramarzi M.A. Larijani B. Hassanzadeh F. Mahdavi M. Design, synthesis, biological evaluation, and molecular modeling studies of pyrazole-benzofuran hybrids as new α-glucosidase inhibitor. Sci. Rep. 2021 11 1 20776 10.1038/s41598‑021‑99899‑1
    [Google Scholar]
  68. Safari S. Ghavimi R. Razzaghi-Asl N. Sepehri S. Synthesis, biological evaluation and molecular docking study of dihydropyrimidine derivatives as potential anticancer agents. J. Heterocycl. Chem. 2020 57 3 1023 1033 10.1002/jhet.3822
    [Google Scholar]
  69. 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. 2017 7 1 42717 10.1038/srep42717 28256516
    [Google Scholar]
  70. Biginelli C.P. Aldehyde-urea derivatives of aceto-and oxaloacetic acids. Gazz. Chim. Ital. 1893 23 1 360 413
    [Google Scholar]
  71. Farooq S. Alharthi F.A. Alsalme A. Hussain A. Dar B.A. Hamid A. Koul S. Dihydropyrimidinones: Efficient one-pot green synthesis using Montmorillonite-KSF and evaluation of their cytotoxic activity. RSC Advances 2020 10 69 42221 42234 10.1039/D0RA09072G 35516739
    [Google Scholar]
  72. Nikam D. Jain A. Vetale S. Bhange A. Jadhav S. Synthesis and evaluation of novel thiophene-dhpms designed having anti-breast cancer potential. Curr. Chem. Lett. 2024 13 4 717 724 10.5267/j.ccl.2024.4.002
    [Google Scholar]
  73. Nikam D. Chaure P. Dhindale L. Bhagat P. Unveiling the impact: A decade review on dihydropyrimidinones (DHPMs) to combat breast cancer. J. Mol. Struct. 2024 1308 138134 10.1016/j.molstruc.2024.138134
    [Google Scholar]
  74. Beck P.S. Leitão A.G. Santana Y.B. Correa J.R. Rodrigues C.V.S. Machado D.F.S. Matos G.D.R. Ramos L.M. Gatto C.C. Oliveira S.C.C. Andrade C.K.Z. Neto B.A.D. Revisiting Biginelli-like reactions: Solvent effects, mechanisms, biological applications and correction of several literature reports. Org. Biomol. Chem. 2024 22 18 3630 3651 10.1039/D4OB00272E 38652003
    [Google Scholar]
  75. Hassan S.F. Rashid U. Ansari F.L. Ul-Haq Z. Bioisosteric approach in designing new monastrol derivatives: An investigation on their ADMET prediction using in silico derived parameters. J. Mol. Graph. Model. 2013 45 202 210 10.1016/j.jmgm.2013.09.002 24080467
    [Google Scholar]
  76. Gour V.K. Yahya S. Shahar Yar M. Unveiling the chemistry of 1,3,4‐oxadiazoles and thiadiazols: A comprehensive review. Arch. Pharm. (Weinheim) 2024 357 1 2300328 10.1002/ardp.202300328 37840397
    [Google Scholar]
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Targeting Breast Cancer: Novel Dihydropyrimidinones As Potent Eg5 
Inhibitors
Bentham Science Publishers ; https://doi.org/10.2174/0115734064336338241112043509
/content/journals/mc/10.2174/0115734064336338241112043509
/content/journals/mc/10.2174/0115734064336338241112043509
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  • Article Type:     Research Article
Keywords: scaffold hopping ; DHPMs ; MCF-7 ; Eg5 inhibitor ; Breast cancer ; Monastrol

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