ABSTRACT
BACKGROUND: One of the most promising strategies to develop multi-targeted anticancer therapeutics is to introduce to the structure of a potential drug two or more pharmacophores (functional groups or structural fragments), which have antiproliferative, proapoptotic or antimetastatic properties acting via different mechanisms. OBJECTIVE: To design, synthesize and perform screening of a novel hybrid anticancer compound. METHOD: A novel hybrid compound 4-[(E)-2-phenylethenesulfonamido]-N-hydroxybutanamide, combining butanehydroxamate and styrenesulfonamide moieties, was designed, synthesized and investigated as a potent antimetastatic and antiproliferative agent. The structure and purity of the synthesized compound were confirmed by 1H NMR, 13C NMR, LC/MS spectroscopy and elemental analysis. The compound was screened for the anticancer activity in vitro against HeLa and in vivo against Lewis lung carcinoma tumor, using an antitumor metalloenzyme inhibitor GM6001 (Ilomastat, Galardin) and Pifithrin-µ as control anticancer agents. RESULTS: It was found that the application of our compound resulted in a high fraction of apoptotic cells in the cell population, along with disruption in the cell cycle profile manifested as arrest of proliferative phases. Furthermore, changes of the morphological properties (i.e., an enhancement of adhesive properties and reduction of the nuclear-to-cytoplasm ratio) were found. The in vivo screening revealed that the compound significantly inhibited the metastasizing process that was manifested by a reduction in the number and volume of metastases. CONCLUSIONS: The obtained results demonstrate that our compound can serve as a base for further structure optimization in order to design new highly-effective antimetastatic and antitumor agents.
Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Design , Drug Evaluation, Preclinical , Drug Screening Assays, Antitumor , Flow Cytometry , HeLa Cells , Humans , Microscopy, Fluorescence , Molecular Structure , Structure-Activity RelationshipABSTRACT
In the title compound, [PdCl2(C5H7N3OS)], the Pd(II) atom adopts a distorted square-planar coordination sphere defined by two N atoms of the bidentate ligand and two Cl atoms. The mean deviation from the coordination plane is 0.029â Å. The methyl group is not coplanar with the plane of the metallacycle [torsion angle C-O-N-C = 20.2â (4)°]. Steric repulsion between the methyl group and atoms of the metallacycle is manifested by shortened intra-molecular Hâ¯C contacts of 2.27, 2.38 and 2.64â Å, as compared with the sum of the van der Waals radii of 2.87â Å. The amino group participates via one H atom in the formation of an intra-molecular N-Hâ¯Cl hydrogen bond. In the crystal, the other H atom of the amino group links mol-ecules via bifurcated N-Hâ¯(Cl,O) hydrogen bonds into chains parallel to [001].
ABSTRACT
In the structure of the title compound, [Cu(C(14)H(11)N(3)OS)(C(5)H(5)N)], the Cu(II) atom exhibits a slightly distorted square-planar CuN(2)OS coordination polyhedron consisting of a phenyl O, an azomethine N and a thio-amide S atom from the tridentate thio-semicarbazonate dianion, and the N atom of a pyridine mol-ecule. The thio-semicarbazonate ligand exists in the thiol tautomeric form as an E isomer. Rotational disorder of the pyridine and phenyl rings in a 1:1 ratio of the respective components is observed. An extensive network of weak N-Hâ¯S, C-Hâ¯O, C-Hâ¯N and C-Hâ¯S hydrogen-bonding inter-actions consolidates the structure.
ABSTRACT
In the title compound, [Cu(C(16)H(11)N(3)O(2)S(2))(C(5)H(5)N)](n), the Cu(II) atom displays a square-pyramidal CuN(2)O(3) coordination geometry with strong elongation in the vertex direction. The hydrazone mol-ecule is coordinated to the Cu(II) atom in a tridentate manner in the enolic form, creating five- and six-membered chelate metallarings. The pyridine mol-ecule completes the square-planar base of the copper coordination environment. The crystal structure displays zigzag polymeric Cu-O-Cu chains along [001]. Several weak π-π inter-actions between benzothia-zole rings were found in the same direction [centroid-centroid distances = 3.7484â (16), 3.7483â (16), 3.6731â (17) and 3.7649â (17)â Å].
ABSTRACT
The title compound, [Pd(C(6)H(4)N(2)S(2))(C(18)H(15)P)(2)], was obtained as a minor product from the reaction of trans-PdCl(2)(PPh(3))(2) with piperazine-1,4-dicarbothioic acid bis-(pyridin-2-yl)amide. The Pd(II) atom displays a slightly distorted square-planar PdP(2)S(2) geometry with a bidentately coordinated pyridin-2-ylcarbonimidodithio-ate ligand and two triphenyl-phosphine mol-ecules, coordinated in cis positions. The crystal structure features weak π-π [centroid-centroid distance =3.7327(15)â Å] and C-Hâ¯π inter-actions and contains an almost spherically shaped void of 50.4â Å(3) per unit cell.
