OJMC  Vol.2 No.4 , December 2012
Antiproliferative Properties of Vinyl Dipeptides: Synthesis and MCF-7 Cell Line Testing
Abstract: Peptide mimics derived with close structure to peptide have vast utility because they are expected to interfere with biological targets while having superior drug-like properties if compared to peptides. In this work, novel vinyl dipeptides which are different in a double bond between the α-carbon of peptide and C1 of its side chain. Added to that, suitable substituents were selected to harness drug-like properties. The compounds were found to have moderate activities when tested against MCF-7 breast cancer cell line. For instance, the adamantyl analogue 2-(benzoylamino)-3-(2-furyl)-N-(1-adamantyl) propenamide (1c) and the heterocyclic analogue 2-(Benzoylamino)-3-(2-furyl)-N-[2-(5-cyanothia-zol-2-yl)] propenamide (1o) exhibited inhibition potency at 27.4 and 37.8 μM, respectively.
Cite this paper: A. Bayoumi, "Antiproliferative Properties of Vinyl Dipeptides: Synthesis and MCF-7 Cell Line Testing," Open Journal of Medicinal Chemistry, Vol. 2 No. 4, 2012, pp. 105-111. doi: 10.4236/ojmc.2012.24013.

[1]   “Cancer/Anticancer Peptides Section, Part VII,” In: A. J. Kasten, Ed., Handbook of Biologically Active Peptides, Academic Press, Waltham, 2006.

[2]   R. M. Freidenger, “Design and Synthesis of Novel Bioactive Peptides and Peptidomimetics,” Journal of Medicinal Chemistry, Vol. 46, No. 26, 2003, pp. 5553-5566. doi:10.1021/jm030484k

[3]   P. B. McKay, M. B. Peters, G. Carta, C. T. Flood, E. Dempsey, A. Bell, C. Berry, D. G. Lloyd and D. Fayne, “Identification of Plasmepsin Inhibitors as Selective Antimalarial Agents Using Ligand Based Drug Design,” Bioorganic & Medicinal Chemistry Letters, Vol. 21, No. 11, 2011, pp. 3335-3341. doi:10.1016/j.bmcl.2011.04.015

[4]   T. T. H. Nguyen, H. Ryu, S. Lee, S. Hwang, V. Breton, J. H. Rhee and D. Kim, “Virtual Screening Identification of Novel Severe Acute Respiratory Syndrome 3C-Like Protease Inhibitors and in Vitro Confirmation,” Bioorganic & Medicinal Chemistry Letters, Vol. 21, No. 10, 2011, pp. 3088-3091. doi:10.1016/j.bmcl.2011.03.034

[5]   Y. K. Peterson, X. S. Wang, P. J. Casey and A. Tropsha, “Discovery of Geranylgeranyltransferase-I Inhibitors with Novel Scaffolds by the Means of Quantitative Structur-Activity Relationship Modeling, Virtual Screening, and Experimental Validation,” Journal of Medicinal Chemistry, Vol. 52, No. 14, 2009, pp. 4210-4220. doi:10.1021/jm8013772

[6]   R. B. Perni, S. C. Conway, S. K. Ladner, K. Zaifert, M. J. Otto and R. W. King, “Phenylpropenamide Derivatives as Inhibitors of Hepatitis B Virus Replication,” Bioorganic & Medicinal Chemistry Letters, Vol. 10, No. 23, 2000, pp. 2687-2690. doi:10.1016/S0960-894X(00)00544-8

[7]   E. M. Al-Arab, B. Ezz, M. Wahid and H. H. Maharram, “Synthesis and Evaluation of Antitumor and Antiviral Screening of Some Newer Aryl Acrylamide Derivatives,” Mansoura Journal of Pharmaceutical Sciences, Vol. 16, 2000, pp. 98-113.

[8]   F. Shi, A. Dai, X. Zhang, B. Jiang and S. Tu, “Facile Diversity-Oriented Synthesis of Novel Dipeptide Mimetic Compounds Containing Bioactive Molecular Skeletons Under Microwave Irradiation,” ACS Combinatorial Science, Vol. 13, No. 2, 2011, pp. 147-153. doi:10.1021/co1000458

[9]   J. Shan and J. J. Zheng, “Optimizing Dvl PDZ Domain Inhibitor by Exploring Chemical Space,” Journal of Computer-Aided Molecular Design, Vol. 23, No. 1, 2009, pp. 37-47. doi:10.1007/s10822-008-9236-1

[10]   J. Peters, “Pharmacological Promiscuity and Molecular Properties,” In: J. Peters, Ed., Polypharmacology in Drug Discovery, Wiley, Hoboken, 2012, pp. 47-59. doi:10.1002/9781118098141.ch3

[11]   S. C. Khadse, G. S. Talele and S. S. Agrawal, “Aminocarbonyl Arylvinylbenzamides as Gastric Sparing Anti-Inflammatory Agents,” Pharmaceutical & Medicinal Chemistry, Vol. 344, No. 5, 2011 pp. 292-300. doi:10.1002/ardp.201000096

[12]   B. H. Banu and K. Bharathi, “Synthesis and Analgesic Activity of Some N-Protected Dehydrophenylalanine Dipeptides,” Journal of Pharmacy Research, Vol. 3, No. 10, 2010, pp. 2450-2452.

[13]   M. S. Mohamed, R. K. Mahmoud, A. I. Sayed and M. E. El-Araby, “Potent Anticonvulsant 1H-Imidazol-5(4H)-One Derivatives with Low Neurotoxicity,” The Open Medicinal Chemistry Journal, Vol. 2, No. 2, 2012, pp. 24-29.

[14]   A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward and D. Forman, “Global Cancer Statistics,” A Cancer Journal for Clinicians, Vol. 61, No. 2, 2011, pp. 69-90. doi:10.3322/caac.20107

[15]   P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J. T. Warren, H. Bokesch, S. Kenney and M. R. Boyd, “New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening,” Journal of the National Cancer Institute, Vol. 82, No. 13, 1990, pp. 1107-1112. doi:10.1093/jnci/82.13.1107

[16]   P. Ertl, B. Rohde and P. Selzer, “Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment Based Contributions and Its Application to the Prediction of Drug Transport Properties,” Journal of Medicinal Chemistry, Vol. 43, No. 20, 2000, pp. 3714-3717. doi:10.1021/jm000942e

[17]   J. J. Luszczki, E. Wojda, M. Andres-Mach, W. Cisowski, M. Glensk, K. Glowniak and S. J. Czuczwar, “Anticonvulsant and Acute Neurotoxic Effects of Imperatorin, Osthole and Valproate in the Maximal Electroshock Seizure and Chimney Tests in Mice: A Comparativestudy,” Epilepsy Research, Vol. 85, No. 2, 2009, pp. 293-299.

[18]   F. Lombardo, B. W. Dominy and P. J. Feeney, “Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings,” Advanced Drug Delivery Reviews, Vol. 46, No. 1-3, 2001, pp. 3-26. doi:10.1016/S0169-409X(00)00129-0

[19]   M. Q. Zhang, “Working with Small Molecules: Rules-of-Thumb of ‘Drug Likeness’,” Methods in Molecular Biology, Vol. 803, 2012, pp. 297-307. doi:10.1007/978-1-61779-364-6_20

[20]   N. Saldabols, A. Treilone, L. N. Alekseeva, B. Brizga and K. Medne, “Synthesis and Transformations of Furan Derivatives. VI. Amides of β-(2-Furyl)- and β-(5-Nitro-2-furyl)-α-acylamidoacrylic Acids and MonoSubstituted 2-Phenyl-4-(5-nitro-2-furfurylidene)-5-imidazolones,” Khimiko-Farmatsevticheskii Zhurnal, Vol. 1, 1967, pp. 21-27.