Synthesis and biological evaluation of conformationally flexible as well as restricted dimers of monastrol and related dihydropyrimidones

European Journal of Medicinal Chemistry

Volumn 46, Issue 8, 2011, Pages 3274-3281

  Kamal, Ahmed ^a   Shaheer Malik, M ^a   Bajee, Shaik ^a   Azeeza, Shaik ^a   Faazil, Shaikh ^a   Ramakrishna, Sistla ^a   Naidu, V G M ^a   Vishnuwardhan, M V P S ^a  

^a INDIAN INSTITUTE OF CHEMICAL TECHNOLOGY   (India)

Author keywords

Anticancer; Antimicrobial; Dihydropyrimidones; Dimers; DNA binding ability; Monastrol

Indexed keywords

ANTIBIOTIC AGENT; DIHYDROPYRIMIDONE DERIVATIVE; DIMER; ETHYL 4 [3 [3 3 [5 (ETHOXYCARBONYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 4 PYRIMIDINYL]PHENOXYPROPOXY]PHENYL] 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 5 PYRIMIDINECARBOXYLATE; ETHYL 4 [3 [4 3 [5 (ETHOXYCARBONYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 4 PYRIMIDINYL]PHENOXY 2 BUTENYL]OXY]PHENYL 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 5 PYRIMIDINECARBOXYLATE; ETHYL 4 [3 [4 3 [5 (ETHOXYCARBONYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 4 PYRIMIDINYL]PHENOXYBUTOXY]PHENYL] 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 5 PYRIMIDINECARBOXYLATE; ETHYL 4 [3 [[5 3 3 [5 (ETHOXYCARBONYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 4 PYRIMIDINYL]PHENOXYPENTYL]OXY]PHENYL] 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 5 PYRIMIDINECARBOXYLATE; ETHYL 4 [4 [4 4 [5 (ETHOXYCARBONYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 4 PYRIMIDINYL] 2 METHOXYPHENOXY 2 BUTENYL]OXY] 3 METHOXYPHENYL 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 5 PYRIMIDINECARBOXYLATE; ETHYL 4 [4 [4 4 [5 (ETHOXYCARBONYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 4 PYRIMIDINYL] 2 METHOXYPHENOXYBUTOXY] 3 METHOXYPHENYL] 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 5 PYRIMIDINECARBOXYLATE; ETHYL 4 [4 [4 4 [5 (ETHOXYCARBONYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 4 PYRIMIDINYL] 2 METHOXYPHENOXYPROPOXY] 3 METHOXYPHENYL] 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 5 PYRIMIDINECARBOXYLATE; ETHYL 4 [4 [[5 4 [5 (ETHOXYCARBONYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 4 PYRIMIDINYL] 2 METHOXYPHENOXYPENTYL]OXY] 3 METHOXYPHENYL] 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 5 PYRIMIDINECARBOXYLATE; METHYL 1 [4 [3 3 [3 [5 [2 (METHOXYCARBONYL)TETRAHYDRO 1H 1 PYRROLYL]CARBONYL 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 4 PYRIMIDINYL]PHENOXY]PROPOXYPHENYL] 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 5 PYRIMIDINYL]CARBONYLTETRAHYDRO 1H 2 PYRROLECARBOXYLATE; METHYL 1 [4 [3 4 [3 [5 [2 (METHOXYCARBONYL)TETRAHYDRO 1H 1 PYRROLYL]CARBONYL 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 4 PYRIMIDINYL]PHENOXY]BUTOXYYPHENYL] 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 5 PYRIMIDINYL]CARBONYLTETRAHYDRO 1H 2 PYRROLECARBOXYLATE; METHYL 1 [4 [3 [5 [3 [5 [2 (METHOXYCARBONYL)TETRAHYDRO 1H 1 PYRROLYL]CARBONYL 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 4 PYRIMIDINYL]PHENOXY]PENTYLOXY]PHENYL] 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDRO 5 PYRIMIDINYL]CARBONYLTETRAHYDRO 1H 2 PYRROLECARBOXYLATE; MONASTROL; PYRIMIDINE DERIVATIVE; PYRROLECARBOXYLATE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ANTIFUNGAL ACTIVITY; ARTICLE; CONFORMATION; CYTOTOXICITY; DENATURATION; DNA BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; NONHUMAN; THERMAL ANALYSIS;

ANTI-INFECTIVE AGENTS; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CELL LINE, TUMOR; COLONIC NEOPLASMS; DIFFERENTIAL THERMAL ANALYSIS; DIMERIZATION; DNA; DRUG SCREENING ASSAYS, ANTITUMOR; FEMALE; GRAM-NEGATIVE BACTERIA; GRAM-POSITIVE BACTERIA; HUMANS; INHIBITORY CONCENTRATION 50; LUNG NEOPLASMS; MICROBIAL SENSITIVITY TESTS; MOLECULAR CONFORMATION; PYRIMIDINES; PYRIMIDINONES; SKIN NEOPLASMS; STRUCTURE-ACTIVITY RELATIONSHIP; THIONES;

EID: 80955179552     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2011.04.048     Document Type: Article

References (28)

1. P. Biginelli Gazz. Chim. Ital 23 1893 360
2. C.O. Kappe Eur. J. Med. Chem. 35 2000 1043
3. C.O. Kappe Tetrahedron 49 1993 6937
4. J.C. Barrow, P.G. Nantermet, H.G. Selnick, K.L. Glass, K.E. Rittle, K.F. Gilbert, R.S.L. Chang, S.S.O. 'Malley, T.V. Olah, J.D. Ellis, A. Barrish, K. Kassahun, D. Nagarathnam, and C.J. Forray J. Med.Chem 43 2000 2703
5. T. Matsuda, and I. Hirao Nippon Kag. Zass 86 1965 1195
6. K.S. Atwal, B.N. Swanson, S.E. Unger, D.M. Floyd, S. Moreland, A. Hedberg, and B.C. O'Reilly J. Med. Chem 34 1991 806
7. G.C. Rovnyak, K.S. Atwal, A. Hedberg, S.D. Kimball, S. Moreland, J.Z. Gougoutas, B.C. O'Reilly, J. Schwartz, and M.F. Malley J. Med. Chem 35 1992 3254
8. G.C. Rovnyak, S.D. Kimball, B. Beyer, G. Cucinotta, J.D. Di-Marco, J. Gougoutas, A. Hedberg, M. Malley, J.P. McCarthy, R. Zhang, and S. Moreland J. Med. Chem 38 1995 119
9. J.C. Barrow, P.G. Nantermet, H.G. Selnick, K.L. Glass, K.E. Rittle, K. Kassahun, P. Leppert, D. Nagarathnam, and C. Forray J. Med. Chem 43 2000 2703
10. D. Nagarathnam, S.W. Miao, C.M. Harrel, and C. Gluchowski J. Med.Chem 42 1999 4764
11. L. Heys, C.G. Moore, and P.J. Murphy Chem. Soc. Rev. 29 2000 57
12. A.D. Patil, N.V. Kumar, W.C. Kokke, M.F. Bean, A.J. Freyer, C. De Brosse, S. Mai, A. Truneh, D.J. Faulkner, B. Carte, A.L. Breen, R.P. Hertzberg, R.K. Johnson, J.W. Westley, and B.C. Potts J. Org. Chem 60 1995 1182
13. C.O. Kappe Acc. Chem. Res. 33 2000 879
14. T.U. Mayer, T.M. Kapoor, S.J. Haggarty, R.W. King, S.L. Schreiber, and T.J. Mitchison Science 286 1999 971
15. T.M. Kapoor, T.U. Mayer, M.H. Coughlin, and T.J.J. Mitchison Cell. Biol. 150 2000 975
16. R. Leizerman, M. Avunie-Masala, M. Elkabets, A. Fich, and L. Gheber Cell. Mol. Life Sci. 61 2004 2060
17. M. Gartner, N. Sunder-Plassmann, J. Seiler, M. Utz, I. Vernos, T. Surrey, and A. Giannis ChemBioChem 6 2005 1173
18. E. Klein, S. DeBonis, B. Thiede, D.A. Skoufias, F. Kozielskib, and L. Lebeaua Bioorg. Med. Chem. 15 2007 6474
19. A. Kamal, D. Dastagiri, M.J. Ramaiah, E.V. Bharathi, C. Srinivas, S.N.C.V.L. Pushpavalli, D. Pal, and M.P. Bhadra ChemMedChem 5 2010 1937
20. A. Kamal, R.V.C.R.N.C. Shetti, S. Azeeza, S.A. Ahmed, P. Swapna, A.M. Reddy, I.A. Khan, S. Sharma, and S.T. Abdullah Eur. J. Med. Chem. 45 2010 4545
21. A. Kamal, Y.V.V. Srikanth, M.N.A. Khan, T.B. Shaik, and M. Ashraf Bioorg. Med. Chem. Lett. 20 2010 5229
22. A. Kamal, G. Ramakrishna, P. Raju, A. Viswanath, M.J. Ramaiah, G. Balakishan, and M.P. Bhadra Bioorg. Med. Chem. Lett. 20 2010 4865
23. A. Kamal, S.F. Adil, R.T. Jaki, B. Siddardha, and U.S.N. Murthy Lett. Drug Des. Discov 6 2009 201
24. C.O. Kappe, and A. Stadler A.Org. React 63 2004 1
25. J. Zhu, and H. Bienaymé Multicomponent Reactions first ed. 2005 Wiley-VCH Weinheim
26. http://www.atcc.org/Portals/1/Pdf/30-1010k.pdf
27. G.B. Jones, C.L. Davey, T.C. Jenkins, A. Kamal, G.G. Kneale, S. Neidle, G.D. Webster, and D.E. Thurston Anti-Cancer Drug Des 5 1990 249
28. J. Azizian, M.K. Mohammadi, O. Firuzi, B. Mirza, and R. Miri Chem. Biol. Drug Des 75 2010 375