A nanohybrid prepared from green source (nanocellulose, NC) and nitrogen, sulfur co-doped graphene quantum dots (N, S@GQDs) was prepared for the electrochemical detection of olanzapine (OLZ), atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. Polar groups on the surface of NC and N, S@GQDs provide more anchoring sites for adsorption of OLZ onto the electrode surface. In addition, it provides high conductivity, good mechanical strength, large surface area, and excellent electrical conductivity. The nanocomposite was characterized morphologically and electrochemically by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDX), transmission electron microscope (TEM), electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square wave adsorptive stripping voltammetry (SWAdSV). Under the optimized conditions, the modified electrode has a good response in the range of 1.5–90.0 × 10−8 M with LOD of 0.5 × 10−8 M. The proposed electrode offers high sensitivity, selectivity, and reliability towards OLZ detection. The SWAdSV was used to determine OLZ in pharmaceutical tablets, human plasma and urine with good recoveries % and reasonable RSD% values.

The interactions of the recent carbapenems; ertapenem (ERP) and meropenem (MRP); with serum albumin (SA) were closely investigated by a combined spectrofluorometric experimental and theoretical approach. The approach is based on the quenching of fluorescence intensity of bovine serum albumin (BSA) upon binding with different carbapenems. The quenching was observed at λem 333–340 nm after excitation at 280 nm. Mechanism of interaction was found to be static quenching through hydrophobic and H-bonding interactions and confirmed with molecular docking using MOE software. Binding constant, binding number were estimated for both MRP and ERP. Thermodynamic parameters including entropy change (ΔS), enthalpy change (ΔH) and free energy change (ΔG) were calculated at three different temperatures. Moreover, BSA configuration during binding was investigated via synchronous and 3D spectrofluorimetry. Förster resonance energy transfer calculated (FRET), integration interval (J) and distance (ro) between BSA and the studied drugs were calculated to confirm the static quenching.

The interactions of the recent carbapenems; ertapenem (ERP) and meropenem (MRP); with serum albumin (SA) were closely investigated by a combined spectrofluorometric experimental and theoretical approach. The approach is based on the quenching of fluorescence intensity of bovine serum albumin (BSA) upon binding with different carbapenems. The quenching was observed at λem 333–340 nm after excitation at 280 nm. Mechanism of interaction was found to be static quenching through hydrophobic and H-bonding interactions and confirmed with molecular docking using MOE software. Binding constant, binding number were estimated for both MRP and ERP. Thermodynamic parameters including entropy change (ΔS), enthalpy change (ΔH) and free energy change (ΔG) were calculated at three different temperatures. Moreover, BSA configuration during binding was investigated via synchronous and 3D spectrofluorimetry. Förster resonance energy transfer calculated (FRET), integration interval (J) and distance (ro) between BSA and the studied drugs were calculated to confirm the static quenching.

The interactions of the recent carbapenems; ertapenem (ERP) and meropenem (MRP); with serum albumin (SA) were closely investigated by a combined spectrofluorometric experimental and theoretical approach. The approach is based on the quenching of fluorescence intensity of bovine serum albumin (BSA) upon binding with different carbapenems. The quenching was observed at λem 333–340 nm after excitation at 280 nm. Mechanism of interaction was found to be static quenching through hydrophobic and H-bonding interactions and confirmed with molecular docking using MOE software. Binding constant, binding number were estimated for both MRP and ERP. Thermodynamic parameters including entropy change (ΔS), enthalpy change (ΔH) and free energy change (ΔG) were calculated at three different temperatures. Moreover, BSA configuration during binding was investigated via synchronous and 3D spectrofluorimetry. Förster resonance energy transfer calculated (FRET), integration interval (J) and distance (ro) between BSA and the studied drugs were calculated to confirm the static quenching.

The interactions of the recent carbapenems; ertapenem (ERP) and meropenem (MRP); with serum albumin (SA) were closely investigated by a combined spectrofluorometric experimental and theoretical approach. The approach is based on the quenching of fluorescence intensity of bovine serum albumin (BSA) upon binding with different carbapenems. The quenching was observed at λem 333–340 nm after excitation at 280 nm. Mechanism of interaction was found to be static quenching through hydrophobic and H-bonding interactions and confirmed with molecular docking using MOE software. Binding constant, binding number were estimated for both MRP and ERP. Thermodynamic parameters including entropy change (ΔS), enthalpy change (ΔH) and free energy change (ΔG) were calculated at three different temperatures. Moreover, BSA configuration during binding was investigated via synchronous and 3D spectrofluorimetry. Förster resonance energy transfer calculated (FRET), integration interval (J) and distance (ro) between BSA and the studied drugs were calculated to confirm the static quenching.

Pyrano[3,2-c]quinoline derivatives have been synthesized and utilized to obtain various new hetero-annulated triazolopyrimidine, containing quinoline, pyran, 1,2,4-triazine and pyrimidine in good yields. Newly synthesized compounds have been characterized by spectral data and elemental analysis. Most of the synthesized compounds showed moderate to weak antiproliferative activity on most cancer cell lines, especially leukemia and breast cancer cell lines. The open chain formimidic acid ethyl ester is slightly more potent than hetero-annulated systems. The most active compounds were further investigated for caspase activation, Bax activation and Bcl-2 down regulation compared to doxorubicin as a standard, and indeed exhibited mainly cell cycle arrest at the Pre-G1 and G2/M phases. The transcription effects of 5a and 5b on the p53 were assessed and compared with the reference doxorubicin. The results revealed an increase of 12-19 in p53 level compared to the test cells and that p53 protein level of 5a and 5b was significantly inductive (991, and 639 pg / mL, respectively) in relation to doxorubicin (1263 pg / mL)

A series of novel thiazolo[3,2-b][1,2,4]-triazoles 3a-n has been synthesized and evaluated in vitro as potential antiproliferative. Compounds 3b-d exhibited significant antiproliferative activity. Compound 3b was the most potent with Mean GI50 1.37 µM comparing to doxorubicin (GI50 1.13 µM). The transcription effects of 3b, 3c and 3d on the p53 were assessed and compared with the reference doxorubicin. The results revealed an increase of 15-27 in p53 level compared to the test cells and that p53 protein level of 3b, 3c and 3d was significantly inductive (1419, 571 and 787 pg / mL, respectively) in relation to doxorubicin (1263 pg / mL). The docking study of the new compounds 3a-n revealed high binding scores for the new compounds toward p53 binding domain in MDM2. The docking analyses revealed the highest affinities for compounds 3b-d which induced p53 activity in MCF-7 cancer cells. Compound 3b which exhibited the highest antiproliferative activity and induced the highest increase in p53 level in MCF-7 cells also showed the highest affinity to MDM2.

A series of novel thiazolo[3,2-b][1,2,4]-triazoles 3a-n has been synthesized and evaluated in vitro as potential antiproliferative. Compounds 3b-d exhibited significant antiproliferative activity. Compound 3b was the most potent with Mean GI50 1.37 µM comparing to doxorubicin (GI50 1.13 µM). The transcription effects of 3b, 3c and 3d on the p53 were assessed and compared with the reference doxorubicin. The results revealed an increase of 15-27 in p53 level compared to the test cells and that p53 protein level of 3b, 3c and 3d was significantly inductive (1419, 571 and 787 pg / mL, respectively) in relation to doxorubicin (1263 pg / mL). The docking study of the new compounds 3a-n revealed high binding scores for the new compounds toward p53 binding domain in MDM2. The docking analyses revealed the highest affinities for compounds 3b-d which induced p53 activity in MCF-7 cancer cells. Compound 3b which exhibited the highest antiproliferative activity and induced the highest increase in p53 level in MCF-7 cells also showed the highest affinity to MDM2.

Introduction: Histone deacetylases (HDACs) represent one of the most validated cancer targets. The inhibition of HDACs has been proven to be a successful strategy for the development of novel anticancer candidates. Methods: This work describes design and synthesis of a new set of HDAC inhibitors (7a-c and 8a, b) utilizing ligustrazine as a novel cap moiety, and achieving the pharmacophoric features required to induce the desired inhibition. Results: The newly synthesized derivatives were evaluated for their potential inhibitory activity toward two class I histone deacetylases, namely HDAC1 and HDAC2. The tested ligustrazine-based compounds were more potent toward HDAC2 (IC50 range: 53.7–205.4 nM) than HDAC1 (IC50 range: 114.3–2434.7 nM). Furthermore, the antiproliferative activities against two HDAC-expressing cancer cell lines; HT-29 and SH-SY5Y were examined by the MTT assay. Moreover, a molecular docking study of the designed HDAC inhibitors (7a-c and 8a,b) was carried out to investigate their binding pattern within their prospective targets; HDAC1 (PDB-ID: 4BKX) and HDAC2 (PDB-ID: 6G3O). Discussion: Compound 7a was found to be the most potent analog in this study toward HDAC1 and HDAC2 with IC50 values equal 114.3 and 53.7 nM, respectively. Moreover, it was the most effective counterpart (IC50 = 1.60 μM), with 4.7-fold enhanced efficiency than reference drug Gefitinib (IC50 = 7.63 μM) against SH-SY5Y cells. Whereas, compound 8a (IC50 = 1.96 μM) was the most active member toward HT-29 cells, being 2.5-times more potent than Gefitinib (IC50 = 4.99 μM). Collectively, these results suggest that 7a merits further optimization and development as an effective new HDACI lead compound

Recent studies have shown additive and synergistic effects associated with the combination of kinase inhibitors. BRAFV600E and EGFR are attractive targets for many diseases treatments and have been studied extensively. In keeping with our interest in developing anticancer targeting EGFR and BRAFV600E, a novel series of 2,3-dihydropyrazino[1,2-a]indole-1,4-dione has been rationally designed, synthesized and evaluated for their antiproliferative activity against a panel of four human cancer cell lines. Compounds 20-23, 28-31, and 33 showed promising antiproliferative activities. These compounds were further tested for their inhibitory potencies against EGFR and BRAFV600E kinases with erlotinib as a reference drug. Compounds 23 and 33 exhibited equipotency to doxorubicin against the four cell lines and efficiently inhibited both EGFR (IC50 = 0.08 and 0.09 µM, respectively) and BRAFV600E (IC50 = 0.1 and 0.29 µM, respectively). In cell cycle study of MCF-7 cell line, compounds 23 and 33 induced apoptosis and exhibited cell cycle arrest in both Pre-G1 and G2/M phases. Molecular docking analyses revealed that the new compounds can fit snugly into the active sites of EGFR, and BRAFV600E kinases. Compound 23, 31 and 33 adopted similar binding orientations and interactions to those of erlotinib and vemurafenib.