Cilazapril Hydrate

Glioblastoma is the most common and most aggressive primary brain cancer in adults. Standard treatment of glioblastoma consisting of maximal safe resection, adjuvant radiotherapy and chemotherapy with temozolomide, results in an overall median survival of 14.6 months. The aggressive nature of glioblastoma has been attributed to the presence of glioblastoma stem cells which express components of the renin-angiotensin system (RAS). This phase I clinical trial investigated the tolerability and efficacy of a treatment targeting the RAS and its converging pathways in patients with glioblastoma. Patients who had relapsed following standard treatment of glioblastoma who met the trial criteria were commenced on dose-escalated oral RAS modulators (propranolol, aliskiren, cilazapril, celecoxib, curcumin with piperine, aspirin, and metformin). Of the 17 patients who were enrolled, ten completed full dose-escalation of the treatment. The overall median survival was 19.9 (95% CI:14.1-25.7) months. Serial FET-PET/CTs showed a reduction in both tumor volume and uptake in one patient, an increase in tumor uptake in nine patients with decreased (n = 1), unchanged (n = 1) and increased (n = 7) tumor volume, in the ten patients who had completed full dose-escalation of the treatment. Two patients experienced mild side effects and all patients had preservation of quality of life and performance status during the treatment. There is a trend towards increased survival by 5.3 months although it was not statistically significant. These encouraging results warrant further clinical trials on this potential novel, well-tolerated and cost-effective therapeutic option for patients with glioblastoma.

For cilazapril (CLZ), analytical methods based on donor-acceptor phenomenon that are simple, rapid with broad linear dynamic range for the quantification of drug are not available in the literature. Considering the requirement for the methods, in this study, two economic, potent analytical methods based on the complexation of CLZ with π-acceptors, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (CA) were developed, validated, and studied spectrophotometrically. Various analytical data were discussed. The effects of experimental variables were optimized from the results of in silico technique, i.e. Box-Behnken design under response surface methodology. Linear dynamic range was significantly good in the range of 6-60 µg mL^-1 and 20-260 µg mL^-1 for DDQ and CA methods. Moreover, molecular docking studies corroborated the experimental results. Further, the methods were supplemented by the pharmaceutical and biological application for the quantitative assay of CLZ. Collectively, the results of the reported method of the analysis suggest that the developed approach is simple, sensitive, accurate and precise.