ABSTRACT
In this research paper, we report the cytotoxic and apoptotic effects of 1,2,3-triazole derivatives in a unique 7a-g or hybrid form with isoxazoline 8a-g using the eugenol as a precursor in HT-1080 fibrosarcoma, MCF-7, and MDA-MB-231 breast carcinoma, and A-549 lung carcinoma. Data obtained on the cytotoxic effects have shown that hybrid compounds 8a-e induced a significant anticancer activity and are more important than the ones of 1,2,3-triazole derivatives 7a-g with IC50 ranging from 18 to 43 µM for the hybrids 8a-e and from 15 to 29 µM for mono-adducts 7a-g in all cell lines. Concerning the apoptotic study, compounds 7b and 8a can induce apoptosis in HT-1080 and A-549 cells as revealed by Annexin-V labeling and caspase-3/7 activity, also, the apoptotic effect was accompanied by cell cycle arrest at G2/M phase in the case of compounds 7b and 8a. Both compounds were evaluated in-silico through molecular docking and molecular dynamics and compound 8a is very active against Bcl-2 protein triggering apoptosis phenomenon by intrinsic pathway, therefore compound 8a is a potential candidate to inhibit the anti-apoptotic protein (Bcl-2).Communicated by Ramaswamy H. Sarma.
Subject(s)
Antineoplastic Agents , Carcinoma , Fibrosarcoma , Humans , Molecular Docking Simulation , Eugenol/pharmacology , Triazoles/chemistry , Cell Line, Tumor , Antineoplastic Agents/chemistry , Apoptosis , Proto-Oncogene Proteins c-bcl-2/metabolismABSTRACT
In the title mol-ecule, C20H21N3O3, the allyl substituent is rotated out of the plane of its attached phenyl ring [torsion angle 100.66â (15)°]. In the crystal, C-HMthphnâ¯OMthphn (Mthphn = meth-oxy-phen-yl) hydrogen bonds lead to the formation of (100) layers that are connected into a three-dimensional network by C-Hâ¯π(ring) inter-actions, together with π-π stacking inter-actions [centroid-to-centroid distance = 3.7318â (10)â Å] between parallel phenyl rings. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from Hâ¯H (48.7%) and Hâ¯C/Câ¯H (23.3%) inter-actions. Computational chemistry reveals that the C-HMthphnâ¯OMthphn hydrogen bond energy is 47.1â kJâ mol-1. The theoretical structure, optimized by density functional theory (DFT) at the B3LYP/ 6-311â G(d,p) level, is compared with the experimentally determined mol-ecular structure. The HOMO-LUMO behaviour was elucidated to determine the energy gap.
ABSTRACT
The asymmetric unit of the title compound, C23H28O4, comprises two half-mol-ecules, with the other half of each mol-ecule being completed by the application of twofold rotation symmetry. The two completed mol-ecules both have a V-shaped appearance but differ in their conformations. In the crystal, each independent mol-ecule forms chains extending parallel to the b axis with its symmetry-related counterparts through C-Hâ¯π(ring) inter-actions. Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from Hâ¯H (65.4%), Hâ¯C/Câ¯H (21.8%) and Hâ¯O/Oâ¯H (12.3%) inter-actions. Optimized structures using density functional theory (DFT) at the B3LYP/6-311â G(d,p) level are compared with the experimentally determined mol-ecular structures in the solid state. The HOMO-LUMO behaviour was elucidated to determine the energy gap.