Synthesis and Evaluation of Cytotoxic Activity of Certain Benzo[h]chromene Derivatives.

BACKGROUND: Benzo[h]chromenes attracted great attention because of their widespread biological activities, including anti-proliferate activity, and the discovery of novel effective anti-cancer agents is imperative. OBJECTIVE: The main objective was to synthesize new benzo[h]chromene derivatives and some reported derivatives, and then test all of them for their anti-cancer activities. METHODS: The structures of the newly synthesized derivatives were confirmed by elemental and spectral analysis (IR, Mass, 1H-NMR and 13C-NMR). 35 compounds were selected by the National Cancer Institute (NCI) for single-dose testing against 60 cell lines and 3 active compounds were selected for 5-doses testing. Also, these 3 compounds were tested as EGFR-inhibitors; using sorafenib as standard, and as Tubulin polymerization inhibitors using colchicines as a standard drug. Moreover, molecular docking study for the most active derivative on these 2 enzymes was also carried out. RESULTS: Compounds 1a, 1c and 2b have the highest activities among all 35 tested compounds especially compound 1c. CONCLUSION: compound 1c has promising anti-cancer activities compared to the used standards and may need further modification and investigations.

Therapeutic effects of regorafenib after sorafenib monotherapy with advanced hepatocellular carcinoma including Child-Pugh classification B: A retrospective observational study.

The therapeutic effect of regorafenib was previously demonstrated in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh classification A (CP-A) whose disease progressed during sorafenib treatment in a phase III trial. However, treatment options are limited for patients with advanced HCC other than CP-A. In this study, we aimed to evaluate the therapeutic effect of regorafenib on advanced HCC patients including those with Child-Pugh classification B (CP-B).We retrospectively analyzed the medical records of 21 patients with advanced HCC who were treated with regorafenib after sorafenib monotherapy at our hospital from July 2017 to April 2018 and were followed up until September 2019. Patients were classified according to liver function and adverse events experienced during sorafenib treatment and were started on regorafenib with a pre-defined reduced starting dose along with a dose reduction and schedule change based on the judgement of the attending physician.At regorafenib initiation, 13 and 8 patients were classified as CP-A and CP-B, respectively. In all patients with CP-B, the starting dose of regorafenib was reduced, and the pre-defined starting-dose sets were applied to 17 (81%) patients. The median duration of regorafenib treatment in patients with CP-A and CP-B were 4.1 months and 2.0 months, respectively, with no significant difference. The median overall survival from regorafenib initiation (OS-r) and sorafenib initiation (OS-s) was 13.2 months and 30.9 months, respectively. In subgroup analysis, OS-r was 16.3 months in patients with CP-A and 10.1 months with CP-B with no significant difference (P = .44), whereas OS-r was 16.3 months in patients with modified albumin-bilirubin Grade 1/2a and 13.2 months in patients with Grade 2b, with no significant difference. There was no clear difference in the incidence rate of ≥grade 3 adverse events between CP-A and CP-B. OS-r and OS-s were significantly correlated.Even patients with impaired liver function achieved the desired therapeutic effects by safely reducing the starting dose of regorafenib according to both impaired liver function and adverse events during pretreatment. Regorafenib may be considered to be an effective treatment after sorafenib monotherapy in patients with impaired liver function.