Synthesis of pyrazoline fatty chain derivatives and its effects on melanoma cells.

Skin cancer is the most common type of cancer in Brazil, representing 30% of all cases. Among these, melanoma represents only 3% of malignant neoplasms; however, it is the most serious and has a high capacity for metastasis. For this reason, it is extremely important to identify more efficient compounds and treatments that stop or decrease the proliferation of melanoma, even in its more advanced stages. This work reports the synthesis and biological evaluation of two homologous series of pyrazoline fatty chain derivatives as potent antitumoral agents in the melanoma B16F10 cell line. Cells were treated with pyrazoline fatty chain compounds (3, 30, 300, and 3000 µM) for 0, 24, 48, and 72 h. Decreased cell viability was observed when using most compounds at different concentrations and times. The structure-activity relationship (SAR) between antitumoral activity and the number of carbons and lipophilicity, as well as the oxygen-sulfur bioisosteric exchange, was evaluated. Among the tested derivatives, the lipophilic compounds 5-hydroxy-5-(trifluoromethyl)-3-undecyl-4,5-dihydro-1H-pyrazole-1-carboxamide (2d) and 5-hydroxy-5-(trifluoromethyl)-3-undecyl-4,5-dihydro-1H-pyrazole-1-thiocarboxamide (3d) showed the best results in the B16F10 cell line, as they produced the best cell viability decrease effects. The presence of fatty unbranched undecyl chain in the molecular structure appears to be important for its antimelanoma properties.

(S,Z)-3-Phenyl-2-[(1,1,1-tri-chloro-7-meth-oxy-2,7-dioxohept-3-en-4-yl)amino]-propanoic acid monohydrate.

In the title compound, C17H18Cl3NO5·H2O, intra-molecular N-H⋯O and C-H⋯Cl hydrogen bonds form S(6) and S(5) ring motifs, respectively. The chiral organic mol-ecule is connected to the solvent water mol-ecule by a short O-H⋯O hydrogen bond. In the crystal, a weak C-H⋯Cl inter-action connects the organic mol-ecules along [100] while the water mol-ecules act as bridges between the organic mol-ecules in both the [100] and [010] directions, generating layers parallel to the ab plane.

2-[5-(2-Methyl-phen-yl)-3-(2-methyl-styryl)-4,5-di-hydro-1H-pyrazol-1-yl]-6-(thio-phen-2-yl)-4-(tri-fluoro-meth-yl)pyrimidine chloro-form monosolvate.

In the crystal structure of the title compound, C28H23F3N4S·CHCl3, the chloro-form solvate mol-ecules connect the pyrimidine mol-ecules into chains along [101] through weak C-H⋯N and C-H⋯Cl hydrogen-bond inter-actions. There are further connections between adjacent chains through F⋯Cl halogen contacts of 3.185 (3) Å, with the -CF3 group presenting a significant short F⋯F inter-chain distance of 2.712 (4) Å. The five-membered pyrazole ring is approximately planar (r.m.s. deviation = 0.050 Å). The pyrimidine ring makes dihedral angles of 84.15 (8) and 4.56 (8)° with the benzene rings.

2-{1-[(6R,S)-3,5,5,6,8,8-Hexamethyl-5,6,7,8-tetra-hydro-naphthalen-2-yl]ethyl-idene}-N-methyl-hydrazinecarbo-thioamide.

The reaction between a racemic mixture of (R,S)-fixolide and 4-methyl-thio-semicarbazide in ethanol with a 1:1 stoichiometric ratio and catalysed with HCl, yielded the title compound, C20H31N3S [common name: (R,S)-fixolide 4-methyl-thio-semicarbazone]. There is one crystallographically independent mol-ecule in the asymmetric unit, which is disordered over the aliphatic ring [site-occupancy ratio = 0.667 (13):0.333 (13)]. The disorder includes the chiral C atom, the neighbouring methyl-ene group and the methyl H atoms of the methyl group bonded to the chiral C atom. The maximum deviations from the mean plane through the disordered aliphatic ring amount to 0.328 (6) and -0.334 (6) Š[r.m.s.d. = 0.2061 Å], and -0.3677 (12) and 0.3380 (12) Š[r.m.s.d. = 0.2198 Å] for the two different sites. Both fragments show a half-chair conformation. Additionally, the N-N-C(=S)-N entity is approximately planar, with the maximum deviation from the mean plane through the selected atoms being 0.0135 (18) Š[r.m.s.d. = 0.0100 Å]. The mol-ecule is not planar due to the dihedral angle between the thio-semicarbazone entity and the aromatic ring, which amounts to 51.8 (1)°, and due to the sp 3-hybridized carbon atoms of the fixolide fragment. In the crystal, the mol-ecules are connected by H⋯S inter-actions with graph-set motif C(4), forming a mono-periodic hydrogen-bonded ribbon along [100]. The Hirshfeld surface analysis suggests that the major contributions for the crystal cohesion are [(R,S)-isomers considered separately] H⋯H (75.7%), H⋯S/S⋯H (11.6%), H⋯C/C⋯H (8.3% and H⋯N/N⋯H (4.4% for both of them).