Some Chemical Aspects of Tetrahydro-1-thiopyran-4-one Derivatives

3,5-Diarylmethylene-2,6-diphenyltetrahydrothiopyran-4-thiones, 2, reacted with two or four moles of bromine to form 3-aryimethylene 5-bromoarylmethylene- 2,6-dipheny1tetrahydrothiopyran- -4-thione, 3, and 3-arylmethylene-5-bromoarylmethylene-2,6-dibromo- 2,6-diphenyltetrahydrothiopyran-4-thione, 5, respectively. Compound 2a reacted with amines giving 2,6-diphenyl-5-iminophenylmethyl- 3-phenylmethylenetetrahydrothiopyran-4-thiones, 6. Diphenydiazomethane and 9-diazofluorene converted 2a into 4-diphenylethylene- 2,6-dipheny1-3,5 diphenylmethylenetetrahydrothiopyran, 7, and 2,6-diphenyl-3,5-diphenylmethylene-4-(9-fluorenylidene) tetrahydrothiopyran, 8, respectively. Compounds 2 with copper-bronze afforded 3,3\u27,5,5\u27-tetraarylmethylene-2,2\u27 ,6,6\u27-tetraphenyl-Lr-thio- 4,4\u27 dipyranylidenes

Practical Needs in Assessing Response to Therapy in Operated Brain High Grade Glioma According to Response Assessment in Neuro-Oncology Criteria

Background: Tumors known as gliomas begin in the brain or spine's glial cells and might spread throughout the body.  An effort was made to improve tumor response evaluation and end point selection through the Response Assessment in Neuro-Oncology (RANO) working group. Objective: To standardize the assessment method and results reporting by applying MRI-RANO criteria in detecting glioma response to surgical treatment. Patients and Methods: This was a prospective cohort study included 12 patients (4 males and 8 females) whose mean age was 53.6 ± 15.1years. Included patients are those who were operated and pathologically proved as brain glioma grade IV (GBM). They underwent post-operative MRI within 48 hours and are available for follow up MRI after 3 months. Imaging modalities applied in both MRI exams were conventional magnetic resonance imaging, MRI diffusion weighted images, and contrast imaging. RANO criteria were applied. Results: According to RANO criteria, none of the lesions had pseudo response or pseudo progression. However, two thirds (66.7%) had progressive disease and one third (33.3%) had complete response. There was statistically significant association between MRI findings 3 months postoperative and RANO criteria as patients with compete response had statistically significant decrease on measurable solid components, diffusion restriction, post contrast enhancement and all lesions had grade I edema with no mass effect or midline shift compared to patients with progressive disease. 4 cases that showed complete response category had fulfilled all the RANO criteria, while 8 cases with category progressive disease had fulfilled more than one of the described RANO criteria. Conclusion: RANO criteria are an effective tool to be used in interpretation of MRI for follow-up of surgically operated glioma patients to detect their response

The correlation between increasing Body Mass Index and the incidence of local recurrence and distant metastasis in breast cancer patients

OBJECTIVE: Patients with breast cancer (BC) who are obese or overweight at the time of diagnosis have a low survival rate and a high death rate. We aimed to investigate if having a higher body mass index (BMI) at diagnosis raised the risk of local recurrence (LR) and distant metastasis. PATIENTS AND METHODS: Patients were divided into three categories based on their BMI. The patient's BMI was determined by dividing his weight in kilograms by his height in square meters (kg/m2). The WHO defines normal weight as 18.5 ≤ BMI < 25 kg/m2, overweight as 25 ≤ BMI < 30 kg/m2, and obesity as BMI ≥ 30 kg/m2. RESULTS: The mean BMI was 30.27±6.06 kg/m2. Out of 250 patients, 60 (24.0%), 73 (29.2%) and 117 (46.8%) patients had normal, overweight and obese BMI respectively. No significant difference between BMI and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) was found, but there was an association between tumor (T) stage and lymph vascular invasion (LVI) (p<0.05). Obese patients had poorer disease-free survival (DFS) and overall survival (OS) than normal and overweight categories (35.38 ±1.72 vs. 42.38 ± 2.79 and 37.82 ± 2.27 months) (39.65±1.65 vs.45.70 ± 2.53 and 44.31 ± 2.04 months) (p<0.001). LR occurs more prevalent in over-weight and obese patients than normal (p<0.03) but there is no significant difference for distant metastasis. CONCLUSIONS: There is a strong negative association between increased BMI and BC prognosis and patient survival; controlling of this phenomenon may improve the response to treatment and survival, therefore health awareness programs should be implemented

Amenability of heap leaching technology on uranium extraction from Gattar and El Missikat area, Eastern Desert, Egypt: A kinetic approach

Studies of uranium heap leaching from different uranium mineralization situated in Eastern Desert of Egypt was investigated via batch experiments, followed by its optimum condition applicationon column percolationtests.The optimum process operating parameters were implemented on large column scale in order to make more condition control and evaluate the time and reagents needed in the large scale. The results show thatleaching efficiency of GIIattained about 78.3% with 34kg/ton acid consumption in a 44 days period, while leaching efficiency of El-Missikat attained about 86.6% with 28kg/ton acid consumption in a 40 days period.Kinetics reaction models of column tests have been investigated to optimize the column leaching behavior. Based on the leaching results of two mineralized samples, the rate of the uranium metal dissolution is controlled by the chemical reaction and the diffusion reaction but diffusion reaction control was more predominate than a chemical reaction control

New Paracyclophanylthiazoles with Anti-Leukemia Activity: Design, Synthesis, Molecular Docking, and Mechanistic Studies

A new series of methyl 2-(2-(4′-[2.2]paracyclophanyl)-hydrazinylidene)-3-substituted-4-oxothiazolidin-5-ylidene)acetates 3a–f were synthesized from the reaction of paracyclophanyl-acylthiosemicarbazides 2a–f with dimethyl acetylenedicarboxylate. Based upon nuclear magnetic resonance (NMR), infrared (IR), and mass spectra (HRMS), the structure of the obtained products was elucidated. X-ray structure analysis was also used as unambiguous tool to elucidate the structure of the products. The target compounds 3a–f were screened against 60 cancer cell lines. They displayed anticancer activity against a leukemia subpanel, namely, RPMI-8226 and SR cell lines. The activity of compound 3a was found as the most cytotoxic potency against 60 cancer cell lines. Consequently, it was selected for further five doses analysis according to National Cancer Institute (NCI) protocol. The cytotoxic effect showed selectivity ratios ranging between 0.63 and 1.28 and between 0.58 and 5.89 at the GI50 and total growth inhibition (TGI) levels, respectively. Accordingly, compound 3a underwent further mechanistic study against the most sensitive leukemia RPMI-8226 and SR cell lines. It showed antiproliferation with IC50 = 1.61 ± 0.04 and 1.11 ± 0.03 µM against RPMI-8226 and SR cell lines, respectively. It also revealed a remarkable tubulin inhibitory activity, compared to colchicine with IC50 = 4.97 µM/mL. Caspase-3, BAX, and Bcl-2 assays for 3a using annexin V-FITC staining revealed significant pro-apoptotic activity. Furthermore, multidrug-resistant leukemia SR cells were used to show better resistance indices (1.285 ng/mL, 1.15-fold) than the reference. Docking studies with β-tubulin indicate that most of the tested compounds illustrated good binding at the colchicine binding site of the enzyme, especially for compound 3a, which made several interactions better than that of the reference colchicine

New Paracyclophanylthiazoles with Anti-Leukemia Activity: Design, Synthesis, Molecular Docking, and Mechanistic Studies

A new series of methyl 2-(2-(4′-[2.2]paracyclophanyl)-hydrazinylidene)-3-substituted-4-oxothiazolidin-5-ylidene)acetates 3a–f were synthesized from the reaction of paracyclophanyl-acylthiosemicarbazides 2a–f with dimethyl acetylenedicarboxylate. Based upon nuclear magnetic resonance (NMR), infrared (IR), and mass spectra (HRMS), the structure of the obtained products was elucidated. X-ray structure analysis was also used as unambiguous tool to elucidate the structure of the products. The target compounds 3a–f were screened against 60 cancer cell lines. They displayed anticancer activity against a leukemia subpanel, namely, RPMI-8226 and SR cell lines. The activity of compound 3a was found as the most cytotoxic potency against 60 cancer cell lines. Consequently, it was selected for further five doses analysis according to National Cancer Institute (NCI) protocol. The cytotoxic effect showed selectivity ratios ranging between 0.63 and 1.28 and between 0.58 and 5.89 at the GI50 and total growth inhibition (TGI) levels, respectively. Accordingly, compound 3a underwent further mechanistic study against the most sensitive leukemia RPMI-8226 and SR cell lines. It showed antiproliferation with IC50 = 1.61 ± 0.04 and 1.11 ± 0.03 µM against RPMI-8226 and SR cell lines, respectively. It also revealed a remarkable tubulin inhibitory activity, compared to colchicine with IC50 = 4.97 µM/mL. Caspase-3, BAX, and Bcl-2 assays for 3a using annexin V-FITC staining revealed significant pro-apoptotic activity. Furthermore, multidrug-resistant leukemia SR cells were used to show better resistance indices (1.285 ng/mL, 1.15-fold) than the reference. Docking studies with β-tubulin indicate that most of the tested compounds illustrated good binding at the colchicine binding site of the enzyme, especially for compound 3a, which made several interactions better than that of the reference colchicine

Design, Synthesis, and Molecular Docking of Paracyclophanyl-Thiazole Hybrids as Novel CDK1 Inhibitors and Apoptosis Inducing Anti-Melanoma Agents

Three new series of paracyclophanyl-dihydronaphtho[2,3-d]thiazoles and paracyclophanyl-thiazolium bromides were designed, synthesized, and characterized by their spectroscopic data, along with X-ray analysis. One-dose assay results of anticancer activity indicated that 3a–e had the highest ability to inhibit the proliferation of different cancer cell lines. Moreover, the hybrids 3c–e were selected for five-dose analyses to demonstrate a broad spectrum of antitumor activity without apparent selectivity. Interestingly, series I compounds (Z)-N-substituted-4,9-dihydronaphtho[2,3-d]thiazol-3(2H)-yl)-4′-[2.2]paracyclophanylamide) that are carrying 1,4-dihydronaphthoquinone were more active as antiproliferative agents than their naphthalene-containing congeners (series II: substituted 2-(4′-[2.2]paracyclophanyl)hydrazinyl)-4-(naphth-2-yl)-thiazol-3-ium bromide hybrids) and (series III: 3-(4′-[2.2]paracyclophanyl)amido-2-(cyclopropylamino)-4-(naphth-2-yl)thiazol-3-ium bromide) toward the SK-MEL-5 melanoma cell line. Further antiproliferation investigations of 3c and 3e on the healthy, normal unaffected SK-MEL-5 cell line indicated their relative safety. Compound 3c showed an inhibition of eight isoforms of cyclin-dependent kinases (CDK); however, it exhibited the lowest IC50 of 54.8 nM on CDK1 in comparison to Dinaciclib as a reference. Additionally, compound 3c revealed a remarkable downregulation of phospho-Tyr15 with a level (7.45 pg/mL) close to the reference. 3c mainly showed cell cycle arrest in the pre-G1 and G2/M phases upon analysis of the SK-MEL-5 cell line. The sequential caspase-3 assay for 3c indicated a remarkable overexpression level. Finally, a molecular docking study was adopted to elucidate the binding mode and interactions of the target compounds with CDK1