Design, synthesis, molecular modelling and antiproliferative evaluation of novel benzothiazole trihybrids.

Colorectal cancer is the third most commonly occurring cancer with very less treatment options in case surgery fails to cure the disease. The emergence of drug resistant colon cancer poses a new threat and calls for better drugs for treatment of colon cancer patients. Novel substituted benzo[d]thiazol-2-yl)-5-(pyridin-2-yl) penta-1,4-dien-3-one trihybrid molecules were synthesized following appropriate synthetic route. These compounds were tested for their efficacy in colon cancer and drug resistant colon cancer cell lines. Their toxicity was studied on the ICR mice model and the selectivity study was performed in calorimetric assay and xenograft mice model. An attempt was also made to chalk out the feasible mechanism of action based on molecular docking and molecular dynamics simulation studies. Compounds 4f, 4h and 4i were found to be highly effective and selective towards the inhibition of the colon cancer and drug resistant colon cancer cell lines and in the xenograft method. Selective compounds from this study can be developed into potential drug candidates for the possible treatment of drug resistant colorectal cancer.

Development and Validation of HPLC and HPTLC Methods for Therapeutic Drug Monitoring of Capecitabine in Colorectal Cancer Patients.

Capecitabine is a prodrug of 5-fluorouracil, employed as a monotherapy or combination chemotherapy agent for treatment of colorectal cancer. Combination therapy of capecitabine consists of oxaliplatin, and hence, it becomes essential to determine that co-administration does not affect its metabolism. High-performance liquid chromatography and high-performance thin-layer chromatography methods were developed and validated to determine the plasma concentration of capecitabine. In this study, blood samples from 12 patients with colorectal cancer were collected and analyzed by both methods with a reference internal standard. Two groups consisting of six patients each were formed: the first group was treated with capecitabine monotherapy, the second group with capecitabine + oxaliplatin combination therapy. The results of analysis from both the methods indicated that there is no significant drug-drug interaction. The co-administration of oxaliplatin did not affect the metabolism of capecitabine. Both assay methods were compared for their sensitivity, robustness and specificity. It was found that both the assay methods were suitable for therapeutic drug monitoring of capecitabine.

A rapid and simple HPTLC assay for therapeutic drug monitoring of capecitabine in colorectal cancer patients.

Capecitabine is a prodrug of 5-flurouracil, employed as a broad spectrum chemotherapeutic agent. It is also used as monotherapy or a combination chemotherapy agent for the treatment of colorectal cancer. Capecitabine is administered in combination with oxaliplatin and hence it is essential to determine that co-administration does not affect its metabolism. To determine the plasma concentration of capecitabine a simple HPTLC method was developed and validated. Blood samples from 12 patients with colorectal cancer were collected and analyzed by the HPTLC method with a reference internal standard. Out of these 12 patients, six were treated with capecitabine monotherapy and another six were treated with capecitabine + oxaliplatin combination therapy. The results of analysis indicated that there was no significant drug-drug interaction and the co-administration of oxaliplatin did not affect the metabolism of capecitabine. This method is sensitive, robust and specific and allows analysis of multiple samples simultaneously, making it suitable for therapeutic drug monitoring of capecitabine.