Organochlorine pesticides (OCPs) are frequently used worldwide as insecticides, fungicides, herbicides and termiticides and have been associated with a variety of cancers in animal and human studies. In the present study, we examined residues of fourteen OCPs in the serum samples of diagnosed cancer patients and healthy residents of Karachi, Pakistan. A random collection of fasting blood samples was carried out from the donors with informed consent. Serum was separated within 2 h of blood collection and was then subjected to extraction with organic solvents followed by purification with florisil column. The final organic extract of each serum sample was processed with Gas Chromatograph coupled with Electron Capture Detector (GC-ECD). OCPs were detected in 97.59% of the cancer cases and 93.75% of the healthy subjects. Mean concentrations of total OCPs (ΣOCPs) was found elevated in the cancer group (0.606 mg/kg) compared with the control group (0.322 mg/kg). Endosulfan was the highest prevalent OCP with a mean concentration of 0.214 mg/kg in the cancer group and 0.166 mg/kg in the control group. The second most prevalent OCP was 4,4-DDE with a mean concentration of 0.131 mg/kg in the cancer group and 0.019 mg/kg in the control group. Highest level of ΣOCPs was detected in the breast cancer cases (20.411 mg/kg) with a mean level of (2.041 mg/kg). In light of the obtained results and available literature on the subject, it has been concluded that OCPs are positively associated with the risk of various cancers in humans.
Cedrus deodara
(deodar) is practically used, as insect repellent, in the northern areas of Pakistan but no data available therefore this study was conducted to evaluate the effectiveness of deodar oil as an alternate of conventional insecticides against the larval pest stage of mealworm beetle (
Tenebrio molitor
), by feeding method. The aim of the study was to investigate the effectiveness of deodar oil as an alternate of conventional insecticides against the larval pest stage of mealworm beetle (
Tenebrio molitor
), by feeding method. All tested chemicals showed efficacy against the pests. The LC
50
was determined by probit analysis and was found to be 3.41, 0.086 and 0.023% of larvae treated with deodar oil, Carbosulfan and Imidacloprid respectively The LC
50
treated larvae were subjected to the evaluation of protein activity, qualitatively and quantitatively. The protein level in tested insects was enhanced when treated with Imidacloprid, Carbosulfan and deodar oil. The electrophoretic profile of treated insects showed more bands in insects treated with
Cedrus deodara
oil. This electrophoretic profile appeared in 4, 5, 7 and 8 bands for tested chemicals including control. Antifeedant activity was observed for
C. deodara
as larvae were deterred to feed on the food found in the container.
Identification of hotspot drug-receptor interactions through in-silico prediction methods (Pharmacophore mapping, virtual screening, 3DQSAR, etc), is considered as a key approach in drug designing and development process. In the current design study, advanced in-silico based computational techniques were used for the identification of lead-like molecules against the targeted receptor β-glucuronidase. The binding pattern of a potent inhibitor in the ligand-receptor X-ray co-crystallize complex was used to identify and extract the structure-base Pharmacophore features. Based on these observations; five structure-based pharmacophore models were derived to conduct the virtual screening of ICCBS in-house data-base. Top-ranked identified Hits (33 compounds) were selected to subject for in-vitro biological activity evaluation against β-glucuronidase enzyme; out of them, twenty compounds (61% of screened compounds) evaluated as actives, however eleven compounds were found to have significantly higher inhibitory activity, including compounds 1, 5–8, 10, 12–13, and 17–19 with IC50 values ranging from 1.2 μM to 34.9 μM. Out of the eleven potent inhibitors, seven compounds 1, 5, 6, 7, 8, 13, and 19 were found new, and evaluated first time for the β-glucuronidase inhibitory activity. Compounds 1, 5 and 19 exhibited a highly potent inhibition in uM of β-glucuronidase enzyme with non-cytotoxic behavior against the mouse fibroblast (3T3) cell line. Our combined in-silico and in-vitro results revealed that the binding pattern analysis of the eleven potent inhibitors, showed almost similar non-covalent interactions, as observed in case of our validated pharmacophore model. The obtained results thus demonstrated that the virtual screening minimizes false positives, and provide a template for the identification and development of new and more potent β-glucuronidase inhibitors with non-toxic effects.
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