QSAR modeling and molecular docking studies of 2-oxo-1, 2-dihydroquinoline-4- carboxylic acid derivatives as p-glycoprotein inhibitors for combating cancer multidrug resistance.

Multidrug resistance (MDR) proteins related to the ATP-binding cassette family are found in a very wide range of human tumors and result in therapeutic failure. The overexpression of efflux pumps such as ABCB1 is one of the mechanisms of MDR. This paper aims to develop a reliable quantitative structure-activity relationship (QSAR) model that best describes the correlation between the activity and the molecular structures in order to predict the inhibitory biological activity towards ABCB1. In this regard, a series of quinoline derivatives of 18 compounds were analyzed using different linear and non-linear machine learning (ML) regression methods including k-nearest neighbors (KNN), decision tree (DT), back propagation neural networks (BPNN) and gradient boosting-based (GB) methods. Their aim is to explain the origin of the activity of these investigated compounds and therefore, design new quinoline derivatives with higher effect on ABCB1. A total of 16 ML predictive models were developed on different number of 2D and 3D descriptors and were evaluated using the coefficient of determination (R2) and the root mean squared error (RMSE) statistical metrics. Among all developed models, A GB-based model in particular catboost achieved the highest predictive quality, with one descriptor, expressed by R2 and RMSE of 95% and 0.283 respectively. Molecular docking studies against the target crystal structure of the outward-facing p-glycoprotein (6C0V) revealed significant binding affinities via both hydrophobic and H-bond interactions with the relevant compounds. The 17 has shown the highest binding energy of -9.22 kcal/mol. Therefore, it can suggest that 17 may prove to be a valuable potential lead structure for the design and synthesis of more potent P-glycoprotein inhibitors for combination used with anti-cancer drugs for cancer multidrug resistance management.

[Pancreatitis of hydatid origin]. / Pancréatite d'origine hydatique.

INTRODUCTION: Hydatic cysts of the liver are known to rupture into the biliary tree, but acute pancreatitis is an uncommon consequence. CASE REPORT: A 30-year-old woman who had undergone cholecystectomy 8 years earlier for gall bladder stones was hospitalized because of acute abdominal pain. Acute pancreatitis was diagnosed. Abdominal sonography showed a hydatic cyst. Fifteen days after admission after normalization of the amylasemia, surgical cure was successful. DISCUSSION: This case demonstrates that hepatic material can migrate via the main bile duct and provoke acute pancreatitis. Fistula drainage via the Oddi sphincter can be successful.

[Penetrating injuries of the abdomen. Results of two classical and selective attitudes in the management of 249 wounds]. / Les plaies pénétrantes de l'abdomen. Résultats des 2 attitudes classique et sélective dans la prise en charge de 249 plaies.

The systematic surgical exploration of each abdominal penetrating wound allows an exact out-come of lesions and an adequate treatment without delay. But these advantages are made upon a possibly 30% negative laparotomy. The selective attitude in the management of these abdominal's wounds has permitted to decrease this rate to 5% with a risk of secondary operation for non primary detected lesions in 5%. Our attitude toward 249 penetrative abdominal's wounds was classic and selectable respectively from 86 to 89 and 90 to 93. The results has confirmed the literature's date and especially has shown no significant difference between the two attitude concerning the morbidity and the mortality.