Molecular docking,PKPD, and assessment of toxicity of few chalcone analogues as EGFR inhibitor in search of anticancer agents

In the present work, molecular docking of the chalcone analogues with receptor EGFR carried out using erlotinib as reference drug is reported. About 15 chalcone analogues were analyzed CHL(1–15). Molecules CHL2, CHL3, CHL9, CHL11, and CHL15 found strong affinity for receptor EGFR exhibiting binding energies ??7.7 kcal/mol, ??7.5 kcal/mol, ??7.6 kcal/mol, ??7.9 kcal/mol, and ??8.1 kcal/mol, respectively, when erlotinib a reference drug exhibits binding energy ??7.6 kcal/mol. Toxicity for molecules was assessed against the cytochromes P450 (CYP) and P-gp using Swiss ADMET. Molecule CHL9 could be a suitable lead compound inhibitor to CYP1A2 followed by CHL2 inhibitor of CYP1A2 and CYP2C9 and CHL15 with a most stable binding affinity of ??8.1 kcal/mol, inhibiting CYP1A2, CYP2C19, and CYP2D6. CHL3 has a binding affinity of ??7.5 kcal/mol, inhibiting all the 05 CYP enzymes (CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4). CHL11 has a binding affinity of ??7.9 kcal/mol, inhibiting CYP1A2, CYP2C19, and CYP2C9. Considering inhibition of CYP family enzymes by molecules, further here we have perform the enrichment analysis to these CYP family enzymes and reported the metabolic pathways which were probably affected by inhibition of these enzymes using EnrichR online enrichment analysis server. The current predictions over these 15 chalcone derivatives will be needed to further investigate in vivo and in vitro conditions to identify the optimum therapeutic efficacy and least toxicity.

     

Functional analysis of repositioned anilide derivatives as anticancer compounds

Off the different types cancers 40% of the population have been observed to be affected by leukemia. Contemporary therapeutics is focusing on generation of new synthetic analogues that can exert maximum positive physiological effect with minimum dosage and negligible deleterious side effects. New generation pharmacists are focusing on such promising effects of Imatinib (a potential anti-cancer drug molecule), Dasatinib, Pelitinib and Nilotinib. The present research study focuses on novel synthesized anilides derivative against BCR-ABL kinase as potential anti-leukemic agent. Validation of the compounds by molecular docking with specific BCR-ABL kinase confirmed their activity. Toxicity prediction of these compounds helped to identify sustainability as therapeutic molecules. The IC₅₀ values were calculated (211 ug, 175 ug, 272ug for compounds A, B, C resp.) and the mode of cell death was gauged by DNA laddering assay. The cells were observed to be induced for programmed cell death. By validating and in-vivo testing of three synthesized compounds, the compound B was observed to be more stable thermodynamically with a potentially vital active site and appears to be a promising anti-leukemic factor. The present research thus lays a preliminary platform in world of pharmaceutics, where these new analogues appear to be efficient, target specific and less toxic molecules.     

Applications of location analysis in agriculture: a survey

This article presents a survey of applications of operations research-based techniques to location problems in agriculture. From the early work in the field to more recent applications, researchers have successfully applied, adapted, and improved theoretical location models to fulfil the field's specific needs. This article discusses earlier work in agricultural location theory starting with the seminal work by von Thünen. It then introduces diverse and innovative applications of location models from the 1950s and 1960s. The authors then identify distinguishing features of location problems in agriculture, and discuss their impact on the analysis. In order to illustrate these features and the variety of operations research-based applications to agricultural location, the article turns to six real-world examples. It then considers, in Conclusion, some of the directions that agricultural location theory may take in the future.     

Minimizing customer order lead-time in a two-stage assembly supply chain

Coordination across different process stages of the supply chain is becoming more common as the information needed for this coordination is easier to obtain and share. With the availability of this information, managers are beginning to recognize that there can be benefits to scheduling processes in a coordinated fashion. Thus, finding good schedules for the entire supply chain has added importance to today’s managers. Coordination of the material as it moves from one stage to the next should lead to improved customer order lead-time performance for the whole chain and thus better customer service overall. We look at a two-stage assembly supply chain with the objective of minimizing the average customer order lead-time. Minimizing lead-time is becoming increasingly important as customers demand quicker response. But beyond this better customer service objective, minimizing lead-time is consistent with keeping inventory costs low. We introduce a number of properties of optimal solutions, results for special problem cases, and a series of lower bounds. We also provide a number of intuitive heuristics for coordinated supply chain scheduling and test them to determine their effectiveness.