ACS Combinatorial Science
Letter
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(b) Mallavadhani, U. V.; Sahoo, L.; Kumar, K. P.; Murty, U. S.
Synthesis and Antimicrobial Screening of Some Novel Chalcones and
Flavanones Substituted with Higher Alkyl Chains. Med. Chem. Res.
2014, 23, 2900−2908. (c) Zangade, S. B.; Jadhav, J. D.; Vibhute, Y. B.;
Dawane, B. S. Synthesis and Antimicrobial Activity of Some New
Chalcones and Flavones Containing Substituted Naphthalene Moiety.
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L. Functionalized Chalcones with Basic Functionalities Have
Antibacterial Activity against Drug Sensitive Staphylococcus aureus.
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(13) (a) Sivakumar, P. M.; Muthu-Kumar, T.; Doble, M. Antifungal
Activity, Mechanism and QSAR Studies on Chalcones. Chem. Biol.
Drug Des. 2009, 74, 68−79. (b) Lahtchev, K. L.; Batovska, D. I.;
Parushev, S. P.; Ubiyvovk, V. M.; Sibirny, A. A. Antifungal Activity of
Chalcones: A Mechanistic Study Using Various Yeast Strains. Eur. J.
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(14) Asad, M.; Beevi, F.; Ganesan, S. P.; Oo, C. W.; Kumar, R. S.;
Laxmipathi, V.; Osman, H.; Ali, M. A. Synthesis of Novel and Highly
Functionalized 4-Hydroxycoumarin Chalcone and their Pyrazoline
Derivatives as Anti-Tuberculosis Agents. Lett. Drug Des. Discovery
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A.; Wei, L. S.; Ahmad, S.; Abas, F.; Ismail, N. H.; Jantan, I.; Wai, L. K.
Inhibition of Prostaglandin E2 Production by Synthetic Minor
Prenylated Chalcones and Flavonoids: Synthesis, Biological Activity,
Crystal Structure, and in Silico Evaluation. Bioorg. Med. Chem. Lett.
2014, 24, 3826−3834. (b) Lee, I.-S.; Lim, J.; Gal, J.; Kang, J. C.; Kim,
H. J.; Kang, B. Y.; Choi, H. Anti-inflammatory Activity of
Xanthohumol Involves Heme Oxygenase-1 Induction via NRF2-ARE
Signaling in Microglial BV2 Cells. J. Neurochem. Int. 2011, 58, 153−
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(5) (a) Galloway, W. R. J. D.; Isidro-Llobet, A.; Spring, D. R.
Diversity-Oriented Synthesis As a Tool for the Discovery of Novel
Biologically Active Small Molecules. Nat. Commun. 2010, 1, 80.
(b) O’Connor, C. J.; Laraia, L.; Spring, D. R. Chemical Genetics.
Chem. Soc. Rev. 2011, 40, 4332−4345. (c) Beckmann, H.; O’ Connor,
C. J.; Spring, D. R. Diversity-Oriented Synthesis: Producing Chemical
Tools for Dissecting Biology. Chem. Soc. Rev. 2012, 41, 4444−4456.
(6) Nadin, A.; Hattotuwagama, C.; Churcher, I. Lead-Oriented
Synthesis: A New Opportunity for Synthetic Chemistry. Angew. Chem.,
Int. Ed. 2012, 51, 1114−1122. (b) MacLellan, P.; Nelson, A. A
Conceptual Framework for Analysing and Planning Synthetic
Approaches to Diverse Lead-like Scaffolds. Chem. Commun. 2013,
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(16) For representative examples, see: (a) Zhang, E.; Wang, R.; Guo,
S.; Liu, B. An Update on Antitumor Activity of Naturally Occurring
Chalcones. J. Evidence-Based Complementary Altern. Med. 2013,
No. 815621. (b) Wang, G.; Peng, F.; Cao, D.; Yang, Z.; Han, X.;
Liu, J.; Wu, W.; He, L.; Ma, L.; Chen, J.; Sang, Y.; Xiang, M.; Peng, A.;
Wei, Y.; Chen, L. Design, Synthesis and Biological Evaluation of
Millepachine Derivatives As a New Class of Tubulin Polymerization
Inhibitors. Bioorg. Med. Chem. 2013, 21, 6844−6854. (c) Kolundija, B.;
Markovi, V.; Stanojkovi, T.; Joksovi, L.; Mati, I.; Todorovi, N.; Nikoli,
(7) For reviews, see: (a) Nandy, J. P.; Prakesch, M.; Khadem, S.;
Reddy, P. T.; Sharma, U.; Arya, P. Advances in Solution- and Solid-
Phase Synthesis toward the Generation of Natural Product-like
Libraries. Chem. Rev. 2009, 109, 1999−2060. (b) Gil, C.; Brase, S.
̈
Solid-Phase Synthesis of Biologically Active Benzoannelated Nitrogen
Heterocycles: An Update. J. Comb. Chem. 2009, 11, 175−197.
(8) (a) Dolle, R. E.; Le Bourdonnec, B.; Goodman, A. J.; Morales, G.
A.; Thomas, C. J.; Zhang, W. Comprehensive Survey of Chemical
Libraries for Drug Discovery and Chemical Biology: 2007. J. Comb.
Chem. 2008, 10, 753−802. (b) Dolle, R. E.; Le Bourdonnec, B.;
Goodman, A. J.; Morales, G. A.; Thomas, C. J.; Zhang, W.
Comprehensive Survey of Chemical Libraries for Drug Discovery
and Chemical Biology: 2008. J. Comb. Chem. 2009, 11, 739−790.
(c) Dolle, R. E.; Le Bourdonnec, B.; Worm, K. A. J.; Morales, G. A.;
Thomas, C. J.; Zhang, W. Comprehensive Survey of Chemical
Libraries for Drug Discovery and Chemical Biology: 2009. J. Comb.
Chem. 2010, 12, 765−806.
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M.; Joksovic, M. D. Novel Anthraquinone Based Chalcone Analogues
Containing an Imine Fragment: Synthesis, Cytotoxicity and Anti-
angiogenic Activity. Bioorg. Med. Chem. Lett. 2014, 24, 65−71.
(d) Abonia, R.; Insuasty, D.; Castillo, J.; Insuasty, B.; Quiroga, J.;
Nogueras, M. Synthesis of Novel Quinoline-2-one Based Chalcones of
Potential Anti-tumor Activity. Eur. J. Med. Chem. 2012, 57, 29−40.
(e) Kumar, D.; Kumar, M.; Akamatsu, K.; Kusaka, E.; Harada, H.; Ito,
T. Synthesis and Biological Evaluation of Indolyl Chalcones As
Antitumor Agents. Bioorg. Med. Chem. 2010, 20, 3916−3919.
(f) Insuasty, B.; Tigreros, A.; Orozco, F.; Quiroga, J.; Abonia, R.;
́
Nogueras, M.; Sanchez, A.; Cobo, J. Synthesis of Novel Pyrazolic
(9) Tsukamoto, T. Tough Times for Medicinal Chemists: Are We to
Blame? ACS Med. Chem. Lett. 2013, 4, 369−370.
(10) Lovering, F.; Bikker, J.; Humblet, C. Escape from Flatland:
Increasing Saturation as an Approach to Improving Clinical Success. J.
Med. Chem. 2009, 52, 6752−6756.
Analogues of Chalcones and Their 3-Aryl-4-(3-aryl-4,5-dihydro-1H-
pyrazol-5-yl)-1-phenyl-1H-pyrazole Derivatives As Potential Antitu-
mor Agents. Bioorg. Med. Chem. 2010, 18, 4965−4974.
(17) For solid-phase synthesis of chalcones, see: (a) Marzinzik, A. L.;
Felder, E. R. Key Intermediates in Combinatorial Chemistry: Access to
Various Heterocycles from α,β-Unsaturated Ketones on the Solid
Phase. J. Org. Chem. 1998, 63, 723−727. (b) Katritzky, A. R.; Serdyuk,
L.; Chassaing, C.; Toader, D.; Wang, X.; Forood, B.; Flatt, B.; Sun, C.;
Vo, K. Syntheses of 2-Alkylamino- and 2-Dialkylamino-4,6-diary-
lpyridines and 2,4,6-Trisubstituted Pyrimidines Using Solid-Phase-
Bound Chalcones. J. Comb. Chem. 2000, 2, 182−185. (c) Katritzky, A.
R.; Chassaing, C.; Barrow, S. J.; Zhang, Z.; Vvedensky, V.; Forood, B.
Solid-Phase Synthesis of 4,6-Disubstituted and 3,4,6-Trisubstituted
Pyrid-2-ones. J. Comb. Chem. 2002, 4, 249−250. (d) Wagman, A. S.;
Wang, L.; Nuss, J. M. Simple and Efficient Synthesis of 3,4-Dihydro-2-
pyridones via Novel Solid-Supported Aza-Annulation. J. Org. Chem.
2000, 65, 9103−9113. (e) Sensfuss, U. Solid-Phase Aldol Con-
densations Mediated by Zinc Acetate and 2,2′-Bipyridine under
(11) (a) Clemons, P. A.; Bodycombe, N. E.; Carrinski, H. A.; Wilson,
J. A.; Shamji, A. F.; Wagner, B. K.; Koehler, A. N.; Schreiber, S. L.
Small Molecules of Different Origins Have Distinct Distributions of
Structural Complexity That Correlate with Protein-Binding Profiles.
Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 18787−18792. (b) Sauer, W. H.
B.; Schwarz, M. K. Molecular Shape Diversity of Combinatorial
Libraries: A Prerequisite for Broad Bioactivity. J. Chem. Inf. Comp. Sci.
2003, 43, 987−1003. (c) Walters, W. P.; Green, J.; Weiss, J. R.;
Murcko, M. A. What Do Medicinal Chemists Actually Make? A 50-
Year Retrospective. J. Med. Chem. 2011, 54, 6405−6416.
(12) For representative examples, see: (a) Joshi, D.; Parikh, K. S.
Synthesis and Antimicrobial Evaluation of 1,3,4-Oxadiazole-Based
Chalcone Derivatives. Med. Chem. Res. 2014, 23, 1855−1864.
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