Abstract
The new antitumor agent anthrafuran has demonstrated a consistent effect in murine tumor models when administered parenterally due to the simultaneous inhibition of multiple cellular targets such as topoisomerases I/II and protein kinases. In this study, we assessed the anticancer efficiency and acute toxicity of anthrafuran administered orally. The action of anthrafuran was studied on transplanted tumor models which included P388 leukemia, Ca755 mammary adenocarcinoma, LLC lung carcinoma, and T47D human breast cancer xenografts on Balb/c nude mice. A significant antitumor efficacy of oral anthrafuran was revealed for all tested tumor models as follows: T/Cmax = 219% for P388, TGImax = 91% for Ca755, TGImax = 84% with CRmax = 54% for LLC, and T/C = 38% for T47D. The optimal treatment schedule of orally administered anthrafuran was 70–100 mg/kg given daily for five days. The LD50 value of orally administered anthrafuran (306.7 mg/kg) in mice was six times higher than that for i.p. administration (52.5 mg/kg). The rates of antitumor efficacy and acute toxicity indicate the high potential for further research on anthrafuran as a new original oral anticancer multitarget agent with an expected satisfactory tolerability and bioavailability.
Highlights
Most anticancer drugs are administered parenterally because this route provides fast and maximal bioavailability, and accurate dosing during the entire course of chemotherapy [1,2]
This study presents the preclinical of the antitumor efficacy in vivoefficacy on leukemia and tumorand models, well results of ainvestigation preclinical investigation of the antitumor in vivo onsolid leukemia solidas tumor as the acute toxicity of anthrafuran after oral administration in mice, while all previous pharmacokinetic models, as well as the acute toxicity of anthrafuran after oral administration in mice, while all and toxicological studies [18,19,20]
The solution was prepared by heating anthrafuran observed only for the◦ single dose of 120 mg/kg
Summary
Most anticancer drugs are administered parenterally because this route provides fast and maximal bioavailability, and accurate dosing during the entire course of chemotherapy [1,2]. Intravenous (i.v.) chemotherapy regimens are generally designed to deliver the maximal tolerable dose of cytotoxic agent, which may lead to hazardous side effects on normal tissues These limitations have shifted the focus in cancer chemotherapy from the i.v. administration to oral therapy, which can be carried out by self-administration [3,4]. Approximately 20–30% of anticancer drugs have formulations for oral administration, and their market share is growing rapidly [5]. Heterocyclic derivatives of anthracenedione efficiently inhibit tumor cell growth demonstrating. Heterocyclic derivativesanthracyclines of anthracenedione efficiently inhibit tumor growth demonstrating advantages over prototype [11] These compounds interactcell with several intracellular advantages over prototype anthracyclines [11]. Anthrafuran is efficient against tumor cells with the molecular molecular determinants of altered drug response as the multidrug resistance(MDR).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
