Correlations between Cytotoxicity and Topography of Some 2-Arylidenebenzocycloalkanones Determined by X-ray Crystallography

Abstract

Three series of 2-arylidenebenzocycloalkanones 1-3 were prepared in order to compare the topography of the molecules with cytotoxicity. These compounds contain two aryl rings whose spatial relationships to each other were influenced by the size of the alicyclic ring and the nature of the substituents in the arylidene aryl rings. All compounds were evaluated against murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. From these results, 1l and 2c,l emerged as useful lead molecules and 1l was shown to significantly inhibit macromolecular DNA, RNA, and protein syntheses in L1210 cells. Various interatomic distances, bond angles, and a torsion angle of 19 representative compounds were determined by X-ray crystallography, and correlations between these data and the cytotoxicity were noted in nearly 40% of the cases examined. Structure-activity relationships revealed that in general, the steric properties of the groups in the arylidene aryl ring, as revealed by measurements of the molar refractivity values, contributed more to bioactivity than the electronic and hydrophobic properties of the aryl substituents. The compounds displayed little murine toxicity, which favors the decision to develop these molecules as cytotoxic and anticancer agents.

Role of Donor−Acceptor Strengths and Separation on the Two-Photon Absorption Response of Cytotoxic Dyes: A TD-DFT Study

“…The family of piperidone and cyclohexanone derivatives (Figure 1b) we considered show significant TPA activities, even though these are not the best cross sections among known organic chromophores. However, compounds 1-17 combine good nonlinear response with important cytotoxic properties [52][53][54][55][56]64 and may, therefore, serve as a synthetic base for future photodynamic therepy drugs.…”

(E)-2-Benzylidenecycloalkanones XII.* Kinetic Measurement of Bovine and Human Serum Albumine Interaction with Selected Chalcones and Their Cyclic Chalcone Analogues by UV Spectrophotometry

“…Compounds 1c, 2b, 4a and 4c were synthesized as described before [4] [5]. Their purity was checked by thin layer chromatography and gas chromatography methods.…”

Assessment of the effect of cyclic chalcone analogues on mitochondrial membrane and DNA

“…In this study we used synthetic cyclic analogues E-2-(4'-methoxybenzylidene)-1-benzosuberone "a" and E-2-(4'-dimethylaminobenzylidene)-1-benzosuberone "b" [2,9,10] (Figure 1) which were synthesized in Pécs, Hungary. Their structures were characterized by IR and NMR spectroscopy.…”

“…It was found that cytotoxity of the individual compounds greatly varied as a function of nature and position of substituents in the particular derivatives. The most cytotoxic of all studied derivatives are benzosuberones with methoxy -and dimethylamino -substituent [2,10].…”