Search

The curcumin analogues (Cur‐MeS and Cur‐MeO) are synthesized using the 3‐chloroacetyl acetone and aromatic aldehydes reaction. Both compounds are characterized using FTIR, LC‐MS, 1H NMR, and 13C NMR spectroscopies. The geometric optimization and thermodynamic properties of the two compounds are carried out theoretically using DFT. The highest HOMO, lowest LUMO, and Mullikan atom charges of the two compounds are calculated using the B3LYP and CAM‐B3LYP methods which are hybrid functionals with a 6‐311+G(2d,p) as the basis set. The nonlinear optical (NLO) properties of both compounds are studied using the spatial self‐phase modulation (SSPM) through the diffraction ring patterns (DRPs) and the Z‐scan techniques, using a continuous wave (cw) low power 473 nm laser beam. The index of nonlinear refraction (INR) of both compounds is calculated by the two techniques. The all‐optical switching property of both samples is tested using two visible cw laser beams. [ABSTRACT FROM AUTHOR]

Background Multidrug resistance (MDR) and drug transporter P-glycoprotein (P-gp) represent major obstacles in cancer chemotherapy. We investigated 19 synthetic curcumin derivatives in drug-sensitive acute lymphoblastic CCRF–CEM leukemia cells and their multidrug-resistant P-gp-overexpressing subline, CEM/ADR5000. Material and methods Cytotoxicity was tested by resazurin assays. Doxorubicin uptake was assessed by flow cytometry. Binding modes of compounds to P-gp were analyzed by molecular docking. Chemical features responsible for bioactivity were studied by quantitative structure activity relationship (QSAR) analyses. A 7-descriptor QSAR model was correlated with doxorubicin uptake values, IC 50 values and binding energies. Results The compounds displayed IC 50 values between 0.7 ± 0.03 and 20.2 ± 0.25 μM. CEM/ADR5000 cells exhibited cross-resistance to 10 compounds, collateral sensitivity to three compounds and regular sensitivity to the remaining six curcumins. Molecular docking studies at the intra-channel transmembrane domain of human P-gp resulted in lowest binding energies ranging from − 9.00 ± 0.10 to − 6.20 ± 0.02 kcal/mol and pKi values from 0.24 ± 0.04 to 29.17 ± 0.88 μM. At the ATP-binding site of P-gp, lowest binding energies ranged from − 9.78 ± 0.17 to − 6.79 ± 0.01 kcal/mol and pKi values from 0.07 ± 0.02 to 0.03 ± 0.03 μM. CEM/ADR5000 cells accumulated approximately 4-fold less doxorubicin than CCRF–CEM cells. The control P-gp inhibitor, verapamil, partially increased doxorubicin uptake in CEM/ADR5000 cells. Six curcumins increased doxorubicin uptake in resistant cells or even exceeded uptake levels compared to sensitive one. QSAR yielded good activity prediction (R = 0.797 and R = 0.794 for training and test sets). Conclusion Selected derivatives may serve to guide future design of novel P-gp inhibitors and collateral sensitive drugs to combat MDR. [ABSTRACT FROM AUTHOR]

A new series of thiosemicarbazones (TSCs) and their 1,3,4-thiadiazolines (TDZs) containing acetamide group have been synthesized from thiosemicarbazide compounds by the reaction of TSCs with cyclic ketones as well as aromatic aldehydes. The structures of newly synthesized 1,3,4-thiadiazole derivatives obtained by heterocyclization of the TSCs with acetic anhydride were experimentally characterized by spectral methods using IR, 1 H NMR, 13 C NMR and mass spectroscopic methods. Furthermore, the structural, thermodynamic, and electronic properties of the studied compounds were also studied theoretically by performing Density Functional Theory (DFT) to access reliable results to the experimental values. The molecular geometry, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) and Mulliken atomic charges of the studied compounds have been calculated at the B3LYP method and standard 6-31+G(d,p) basis set starting from optimized geometry. The theoretical 13 C chemical shift results were also calculated using the gauge independent atomic orbital (GIAO) approach and their respective linear correlations were obtained. [ABSTRACT FROM AUTHOR]