Two divergent series of novel chalcone analogs, one derived from 1-cyclohexylpyrrolidin-2-one and the other derived from 1-benzo[f]chromanone, were designed, synthesized and evaluated for cytotoxicity against two murine cancer cell lines. Two 1-benzo[f]chromanone analogs, 4g and 4j yielded moderate toxicity against both melanoma B16 and lymphoma L1210 cell lines with IC(50) values between the range of 5 and 6 µM. With an IC(50) value of 3.4 µM, compound 4g was also active against human MDA-MB-435 melanoma cells. X-ray structures of the β-hydroxy ketone product (4a) and the α,β-unsaturated ketone (4h) were collected, and confirm the syn-configuration between the carbonyl moiety and the β-vinylic proton in 4h. X-ray structures of two 1-cyclohexylpyrrolidin-2-one derivatives were also obtained, and both showed an E-configuration for the double bond.

The title compound, C22H16N2OS, is a chalcone analog with a thia­zolidinone core that was synthesized as a potential cytotoxic and anti­cancer agent. The structure is commensurately modulated by unit-cell doubling along the direction of the a axis of the cell. The two crystallographically independent mol­ecules are differerentiated by the dihedral angle between the mean planes of the benzyl­idene phenyl group against the thia­zolidin-4-one moiety, which is 5.01 (7)° in one mol­ecule, and 17.41 (6)° in the other. The two mol­ecules are otherwise close to being indistinguishable and are related by crystallographic pseudo-translation. The two mol­ecules are not planar but are slightly bent with the benzyl­idene and phenyl­imino substituents being bent upwards with respect to the center planes of the two mol­ecules. The degree of bending of the two halves of the thia­zolidin-4-one moieties (defined as the planes that inter­sect at the S atom) are 11.08 (7) and 15.88 (7)°. Packing of the mol­ecules is facilitated by C—H⋯π inter­actions and slipped π–π stacking between one of the phenyl rings and a neighboring ethylene π system [distance between the centroid of the ethylene group and the closest phenyl C atom = 3.267 (2) Å, Cg(phenyl)⋯Cg(ethylene) = 3.926 Å].

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Forty-four novel chalcone-inspired analogs having a 3-aryl-2-propenoyl moiety derived from alicyclic ketones were designed, synthesized, and investigated for cytotoxicity against murine B16 and L1210 cancer cell lines. The analogs belong to four structurally divergent series, three of which (series g, h, and i) contain differently substituted cyclopentanone units and the fourth (series j) contains a 3,3-dimethyl-4-piperidinone moiety. Of these, the analogs in series j showed potential cytotoxic activity against murine B16 (melanoma) and L1210 (lymphoma) cells. The most active compounds 5j, 11j, 15j, and 12h produced IC(50) values from 4.4 to 15 μm against both cell lines. A single-crystal X-ray structure analysis and molecular modeling studies confirmed that these chalcones have an E-geometry about the alkene bond and possess a slightly 'twisted' conformation similar to that of combretastatin A-4. At a concentration of 30 μm, compounds 5j, 11j, and 15j did not cause microtubule depolymerization in cells, suggesting that they have a different mechanism of action.