Localization of Deformed Wing Virus (DWV) in the Brains of Apis mellifera (European Honey Bees)

The purpose of the current research project is to design a successful in-situ hybridization to identify regions within the brains of honeybees where DWV replicates. The localization of the virus in the brains of the bees can draw a connection between CCDand DWV.In conclusion, these results demonstrate that in bees infected with DWV the virus replicates actively in very important regions of the brain, including neuropils that are responsible for vision and olfaction. This means that the virus could adversely affect the vision and olfaction of the honeybees making it difficult for bees to behave normally

Identification of chalcone derivatives as putative non-steroidal aromatase inhibitors potentially useful against breast cancer by molecular docking and ADME prediction

283-293Aromatase is an influential target to overcome estrogen receptor positive breast cancer, as the enzyme is responsible for conversion of androstenedione to estrone, a promising drug target for therapeutic management of breast cancer. Chalcones are prominent biosynthetic compounds and parent candidate for the synthesis of heterocycles with diversified biological activities. The prime objective of the present study is to evaluate the binding interaction of 2-hydroxyphenyl- prop-2-en-1-one (1A-1X), 2-hydroxy-4-methoxyphenyl- prop-2-en-1-one (3A-3X), 2,4-dihydroxyphenyl- prop-2-en-1-one (9A-9X) and 1-hydroxynaphthalen-2-yl-prop-2-en-1-one (5A-5X) derivatives with aromatase enzyme by molecular docking study and also check their ADME properties by maestro suit. The designed chalcones derivatives have been docked against our target protein with PDB id 3S7S retrieved from the protein data bank, whereas exemestane has been taken as the positive control. As docking data revealed that docking score of 1K, 1U, 1B 3K 3N, 5K, 5U, 9S, 9K, 9N and 9F compounds found less than exemestane and all of these compounds with appropriate ADME properties have proven their excellent absorption as well as solubility characteristics. The present findings provided valuable information about binding interactions of chalcones derivatives to the active site of aromatase. These compounds may serve as potential lead compound for developing new aromatase inhibitors in breast cancer treatment

Identification of chalcone derivatives as putative non-steroidal aromatase inhibitors potentially useful against breast cancer by molecular docking and ADME prediction

Aromatase is an influential target to overcome estrogen receptor positive breast cancer, as the enzyme is responsible for conversion of androstenedione to estrone, a promising drug target for therapeutic management of breast cancer. Chalcones are prominent biosynthetic compounds and parent candidate for the synthesis of heterocycles with diversified biological activities. The prime objective of the present study is to evaluate the binding interaction of 2-hydroxyphenyl- prop-2-en-1-one (1A-1X), 2-hydroxy-4-methoxyphenyl- prop-2-en-1-one (3A-3X), 2,4-dihydroxyphenyl- prop-2-en-1-one (9A-9X) and 1-hydroxynaphthalen-2-yl-prop-2-en-1-one (5A-5X) derivatives with aromatase enzyme by molecular docking study and also check their ADME properties by maestro suit. The designed chalcones derivatives have been docked against our target protein with PDB id 3S7S retrieved from the protein data bank, whereas exemestane has been taken as the positive control. As docking data revealed that docking score of 1K, 1U, 1B 3K 3N, 5K, 5U, 9S, 9K, 9N and 9F compounds found less than exemestane and all of these compounds with appropriate ADME properties have proven their excellent absorption as well as solubility characteristics. The present findings provided valuable information about binding interactions of chalcones derivatives to the active site of aromatase. These compounds may serve as potential lead compound for developing new aromatase inhibitors in breast cancer treatment

Molecular modeling and ADMET predictions of flavonoids as prospective aromatase inhibitors

192-200With the advent of a myriad of treatment possibilities for breast cancer, enzyme inhibition turns out to be the prevailing strategy for inhibiting estrogen biosynthesis. Aromatization of ring A of androstenedione, testosterone and 16-hydroxytestosterone results in increased estrogen level, which embraces the risk for breast cancer. In this present research, we have targeted human placental aromatase complexed with HDDG046 (PDB ID: 4GL7) for its inhibition by several inhibitors of flavonoid derivatives and further screening those molecules for ADMET properties for assessing its credibility for acceptance in successive steps of drug discovery. Novel flavonoid derivative molecules have been designed using Maestro 10.4, based on the literature review. Further, their molecular modeling studies have been performed against the imported target PDB ID: 4GL7 using the GLIDE platform and have been subjected to ADMET assessment using the QikProp and pkCSM program. From all the series exposed to molecular modeling; 2K, 4K, 6K, 8W and 10K molecules have been subjected to ADMET study based on their interaction profile. Successively screening of these molecules led to selection of 8W molecule for further validation by pkCSM. The results obtained have been compared with the reported molecule HDDG046 which presents substantially positive outcomes for 8W in terms of CaCo2 permeability, water solubility, P- glycoprotein; hERG I, II and CYP interactions, hepatotoxicity, LD50 value and so forth. Juxtaposing the results of all the designed molecules under study, we have established that these prospective molecules especially 8W of flavonoid derivatives have the potency to inhibit the target under study, which can be useful in the treatment of breast cancer. This has been estimated based on the in silico approaches performed using Molecular Modeling which utilizes the integral function of Molecular Mechanics and Quantum Mechanics. In addition, the ADMET predictions validate their integrity for being the lead molecules in drug discovery stages in the near future

Molecular modeling and ADMET predictions of flavonoids as prospective aromatase inhibitors

With the advent of a myriad of treatment possibilities for breast cancer, enzyme inhibition turns out to be the prevailing strategy for inhibiting estrogen biosynthesis. Aromatization of ring A of androstenedione, testosterone and 16a-hydroxytestosterone results in increased estrogen level, which embraces the risk for breast cancer. In this present research, we have targeted human placental aromatase complexed with HDDG046 (PDB ID: 4GL7) for its inhibition by several inhibitors of flavonoid derivatives and further screening those molecules for ADMET properties for assessing its credibility for acceptance in successive steps of drug discovery. Novel flavonoid derivative molecules have been designed using Maestro 10.4, based on the literature review. Further, their molecular modeling studies have been performed against the imported target PDB ID: 4GL7 using the GLIDE platform and have been subjected to ADMET assessment using the QikProp and pkCSM program. From all the series exposed to molecular modeling; 2K, 4K, 6K, 8W and 10K molecules have been subjected to ADMET study based on their interaction profile. Successively screening of these molecules led to selection of 8W molecule for further validation by pkCSM. The results obtained have been compared with the reported molecule HDDG046 which presents substantially positive outcomes for 8W in terms of CaCo2 permeability, water solubility, P- glycoprotein; hERG I, II and CYP interactions, hepatotoxicity, LD50 value and so forth. Juxtaposing the results of all the designed molecules under study, we have established that these prospective molecules especially 8W of flavonoid derivatives have the potency to inhibit the target under study, which can be useful in the treatment of breast cancer. This has been estimated based on the in silico approaches performed using Molecular Modeling which utilizes the integral function of Molecular Mechanics and Quantum Mechanics. In addition, the ADMET predictions validate their integrity for being the lead molecules in drug discovery stages in the near future