Article

Synthesis, molecular modeling and biological evaluation of chalcone thiosemicarbazide derivatives as novel anticancer agents

State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
European Journal of Medicinal Chemistry (Impact Factor: 3.43). 07/2011; 46(9):4702-8. DOI: 10.1016/j.ejmech.2011.07.016
Source: PubMed

ABSTRACT A series of novel chalcone thiosemicarbazide derivatives (4a-4x) have been designed, synthesized, structurally determined, and their biological activities were also evaluated as potential EGFR kinase inhibitors. All the synthesized compounds are first reported. Among the compounds, compound 4r showed the most potent biological activity (IC(50) = 0.78 ± 0.05 μM for HepG2 and IC(50) = 0.35 μM for EGFR), which is comparable to the positive controls. Docking simulation was also performed to position compound 4r into the EGFR active site to determine the probable binding model. Antiproliferative assay results demonstrated that some of these compounds possessed good antiproliferative activity against HepG2. Compound 4r with potent inhibitory activity in tumor growth inhibition may be a potential anticancer agent.

1 Follower
 · 
217 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chalcones (1,3-diaryl-2-propen-1-ones) and their heterocyclic analogues, belong to the flavonoid family, which possess a number of interesting biological properties such as antioxidant, cytotoxic, anticancer, antimicrobial, antiprotozoal, antiulcer, antihistaminic and anti-inflammatory activities. Several pure chalcones have been approved for clinical use or tested in humans. Clinical trials have shown that these compounds reached reasonable plasma concentration and are well-tolerated. For this reason they are an object of continuously growing interest amongst the scientists. However, much of the pharmacological potential of chalcones is still not utilized. The purpose of this review is to provide an overview of the pharmacological activity of naturally occurring and synthetic chalcones. This review highlights more recent pharmacological screening of these compounds, their mechanisms of action and relevant structure-activity relationships.
    Current Medicinal Chemistry 01/2012; 19(2):209-25. DOI:10.2174/092986712803414132 · 3.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Two independent mol-ecules comprise the asymmetric unit of the title compound, C(13)H(19)N(3)OS, which differ in the conformations of the residues linking the thio-urea and the terminal benzene ring, as manifested in the C(m)-C(m)-C(a)-C(a) torsion angles [78.03 (16) and -93.64 (16)°, respectively; m = methyl-ene and a = aromatic]. The dihedral angles [84.40 (4) and 88.28 (5)°] formed between the thio-urea residue and the benzene ring indicate an almost orthogonal relationship. In each thio-urea residue, the N-H hydrogen atoms are anti, and the terminal N-H hydrogen atom forms an intra-molecular N-H⋯N hydrogen bond with the imine-N atom. In each case, the conformation about the imine C=N double bond [1.2812 (17) and 1.2801 (17) Å] is E. In the crystal, the mol-ecules are connected by N-H⋯S hydrogen bonds and these are connected into four mol-ecule aggregates via N-H⋯O hydrogen bonds, which are assembled into a two-dimensional array parallel to (011) via C-H⋯π and π-π inter-actions [ring centroid-centroid distance = 3.8344 (9) Å].
    Acta Crystallographica Section E Structure Reports Online 05/2012; 68(Pt 5):o1461-2. DOI:10.1107/S160053681201611X · 0.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The title compound C(8)H(15)N(3)S has two mol-ecules in the asymmetric unit in which cis-trans isomerism is exhibited around the N(NH)C=S bonds. The cyclo-hexyl rings in both mol-ecules adopt a chair conformation. In the crystal, N-H⋯S hydrogen bonding produces dimers, which are inter-connected through further N-H⋯S hydrogen bonds, forming chains along the b-axis direction.
    Acta Crystallographica Section E Structure Reports Online 11/2012; 68(Pt 11):o3104-5. DOI:10.1107/S1600536812042018 · 0.35 Impact Factor
Show more