Compounds (IIIb), (IIIc), and (IIIe) exhibit significant DNA damage in MCF-7 cells. -(MANJULA, S. N.; NOOLVI, N. M.; PARIHAR, K. V.; REDDY, S. A. M.; RAMANI, V.; GADAD, A. K.; SINGH, G.; KUTTY, N. G.; RAO*, C. M.; Eur.
A B S T R A C T OBJECTIVE:The 2, 3, 7-trisubstituted quinazoline derivatives (Compound HP1, HP2, HP3 and HP4) in two different concentrations were evaluated for antitumor activity against Ehrlich ascites carcinoma (EAC) and Dalton's lymphoma ascites (DLA) bearing Swiss albino mice.
METHODS:The in vivo antitumor potency of quinazoline bases was measured in EAC model by assessing the increase in mean survival time of the treated drug over untreated control mice and treated standard (Gefitinib) mice. Their toxicity was assessed in vivo in normal, standard and EAC bearing mice by measuring the drug-induced changes in haematological parameters. The in vivo antitumor potency of quinazoline bases was assessed in DLA model by measuring solid tumor volume, solid tumor weight and % inhibition of the tumor weight of the treated drug over untreated control mice and treated standard (Gefitinib) mice.
RESULTS:Among the four quinazoline bases studied, HP1, HP3 and HP4 at a dose of 10mg/kg and 20 mg/kg, optimally inhibited the growth of EAC and DLA cells in vivo. Besides, the treatment with HP1 and HP3 (20 mg/kg) significantly restored the deviated haematological parameters in EAC challenged mice. In vivo result authenticates that compound HP3 at a dose of 20mg/kg was most effective. The apoptotic studies shows that, both HP1 and HP3, at 10 and 20 mg/kg body weight showed induction of apoptosis as they significantly restored the deviated haematological parameters in EAC challenged mice.
CONCLUSIONS:Further studies are required to explore the mechanism of action of this novel molecule which might bring gifted outcomes in cancer chemotherapy.
Original ArticleAmerican Journal of Pharmacology and Pharmacotherapeutics www.imedpub.com Keywords: Dalton's lymphoma ascites (DLA), Ehrlich's ascites carcinoma (EAC), Epidermal growth factor receptor (EGFR), Gefitinib, Quinazolines, Tyrosine kinase (TK).
INTRODUCTIONIn spite of the remarkable advances made by medical sciences during the present century, cancer still remains as chief menace against human race. Extensive advancement has been made to fight against cancer; however conventional cancer chemotherapy is highly inadequate due to lack of selectivity between cancer cells and normal cells.1 This calls for novel cancer therapies for selectively targeting cancers without toxicity to normal tissues. The discovery of novel anti-cancer agents that will hopefully provide the desired degree of selectivity for cancer cells versus normal tissues has been filled by the unveiling of a host of novel potential molecular targets through the application of molecular biology approaches to cancer biology.2 Many small molecules inhibitor showed the promising result, of which selective epidermal growth factor receptor (EGFR) inhibitors like quinazolines fitted best in the pocket.3 EGFR inhibitors are anticipated to have great therapeutic potential in the management of malignant and nonmalignant epithelial diseases. 4,5 Quinazolines arose as novel molecules for inhibition of a diverse range of receptor ty...
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