Computer-aided design of selective Cytochrome P450 inhibitors and docking studies of alkyl resorcinol derivatives

The present investigation is aimed to understand the interactive mechanism that occurs between the active site of Cytochrome P450 and its inhibitors by molecular modeling studies. Based on the docking studies and information obtained from interaction analysis, structure-based virtual screening was performed by selecting 217 new potential inhibitors with structural diversity using GOLD and ArgusLab molecular docking softwares. Among a total of 217 compounds, only 21 molecules were considered as the potential inhibitors. Hydrogen bond and van der Waals interaction between various active site residues like ARG 382, HIS447, CYS449, ASN493, TYR131, and TYR92 of Cytochrome P450 were observed. Docking studies of selected resorcinols showed an optimal molecular environment which is required to bind with active sites of Cytochrome P450. Hydroxyl groups of resorcinols exhibited van der Waals interactions with certain active sites. To estimate the drug-likeness properties the parameters like partition coefficient (log P), tabulated molecular polar surface area (TPSA), and bio activity score were obtained from the Molinspiration studies. Based on docking and Molinspiration data analysis, the molecules 10, 3, 18, 19, and 7 were found to be highly potent inhibitors of Cytochrome P450.     

Holy Basil leaf extract decreases tumorigenicity and metastasis of aggressive human pancreatic cancer cells in vitro and in vivo: Potential role in therapy

There is an urgent need to develop alternative therapies against lethal pancreatic cancer (PC). Ocimum sanctum (“Holy Basil”) has been used for thousands of years in traditional Indian medicine, but its anti-tumorigenic effect remains largely unexplored. Here, we show that extracts of O. sanctum leaves inhibit the proliferation, migration, invasion, and induce apoptosis of PC cells in vitro. The expression of genes that promote the proliferation, migration and invasion of PC cells including activated ERK-1/2, FAK, and p65 (subunit of NF-κB), was downregulated in PC cells after O. sanctum treatment. Intraperitoneal injections of the aqueous extract significantly inhibited the growth of orthotopically transplanted PC cells in vivo (p < 0.05). Genes that inhibit metastasis (E-cadherin) and induce apoptosis (BAD) were significantly upregulated in tumors isolated from mice treated with O. sanctum extracts, while genes that promote survival (Bcl-2 and Bcl-xL) and chemo/radiation resistance (AURKA, Chk1 and Survivin) were downregulated. Overall, our study suggests that leaves of O. sanctum could be a potential source of novel anticancer compounds in the future.     

Symptomatic gastroesophageal reflux disease after lung transplantation

Purpose  

Gastroesophageal reflux disease (GERD) is associated with allograft dysfunction after lung transplantation (LTX). We attempted to identify outcomes in LTX recipients with clinical evidence of GERD.     

Congenital heart disease manifested as acute abdominal pain

We present a case of a 53-year-old man with complaints of severe abdominal pain and nausea. Emergency department abdominal workup was non-diagnostic. Physical examination revealed signs of right- and left-heart failure. A past medical history of dysrhythmias and chronic abdominal complaints prompted hospital admission. Subsequent right heart catheterization revealed a significant left-to-right shunt. CT scan of the chest and angiography confirmed the diagnosis of an abnormal ascending vein between the innominate vein and the left superior pulmonary vein. After the anomalous vein was ligated, the patient's abdominal pain resolved.