Benzosuberene-sulfone analogues synthesis from Cedrus deodara oil and their therapeutic evaluation by computational analysis to treat type 2 diabetes.

Benzosuberene-sulfone (BSS) analogues have been semi-synthesized following green approaches from himachalenes, which has been extracted from essential oil of Cedrus deodara. In this process, benzosuberene in presence of different aryl or alkyl sodium sulfinates, I2 and potassium persulfate (K2S2O8) in acetonitrile-water solvent conditions gave BSS-analogues at room temperature. Under this reaction, a facile endocyclic ß-H elimination has been noticed for BSS-analogues synthesis instead of vinyl sulfones and the reason may be due to its specific structure and electronic environment. The BSS-compounds were obtained with moderate to excellent yields under mild conditions. All the compounds were computationally subjected to drug likeliness and toxicity prediction studies. Further, the synthesized molecules were evaluated under in-silico studies for their binding affinity towards the native Peroxisome Proliferator-Activated Receptor Gamma (PPARG), and two PPARG mutants (R357A and V290M). Both the mutant forms of PPARG are deficient in eliciting a response to treatment with full and partial agonists. Our computational studies suggested that the molecule 3q performed better than the standard drug (Rosiglitazone) in all three protein structures. This implies that our suggested molecule could act as a more potent antagonist to native PPARG and could also be developed to treat type-2 diabetes patients with R357A and V290M mutations, which didn't elicit any response to currently available drugs in the market.

Prostate specific antigen ratio: for diagnosis and assessment of aggressiveness of malignancy of prostate.

The search for a perfect tumour marker, which would be able to distinguish benign from malignant enlargement of prostate accurately, is still not complete. Total Prostate Specific Antigen (TPSA), a good test, has it's own inadequacies but Free Prostate Specific Antigen (FPSA) to TPSA ratio is emerging as a better adjuvant to it. This prospective study was done to verify the utility of FPSA to TPSA ratio in diagnosis of malignancy of prostate and its relationship to Gleason grading (indicating the aggressiveness) of adenocarcinoma of prostate. 100 patients with urinary symptoms, who were above fifty years of age and had prostatic enlargement, formed the study group. TPSA and FPSA were assayed by ELISA method and FPSA to TPSA ratio was calculated. Prostatic biopsy of all the cases was obtained and diagnostic histopathology and Gleason grading (in cases where adenocarcinoma was diagnosed) was done. Sensitivity, specificity, predictive value of positive test and predictive value of negative test for TPSA and FPSA to TPSA ratio were calculated. They were found to be 100%, 76.7%, 74.1% and 100% for TPSA and 82%, 100%, 100%, 89% for FPSA/TPSA ratio. Thus making it very obvious that FPSA to TPSA ratio is an excellent adjuvant to TPSA for diagnosis of malignancy of prostate increasing the specificity and predictive value for positive test. An inverse correlation (correlation coefficient = -0.95) was also found between PSA ratio and aggressiveness of prostate cancer, pointing towards its capability to predict the histological (Gleason) grade of the tumour.

Caroli's disease.

Caroli's disease is a rare congenital disorder and occasional cases have been reported from Japan and other parts of Asia. It comprises of congenital dilation of the lower (segmental) intrahepatic bile duct. Cholangitis liver, cirrhosis and cholangiocarcinoma are its potential complication. A case of caroli's disease in an 8-years-old boy with bilobar involvement of liver, (specially affecting right superior lobe) presenting with intermittent abdominal pain, fever and hepatosplenomegaly is reported here.