Study on the immunopathologic effects of 4(3H)-quinazolinone-2-ethyl-2-phenyl ethyl (QEPE) in newborn Balb/C mice

Document Type : Research Articles


1 Zabol University

2 Shahid-Beheshti University


Quinazolinones are heterocyclic and water insoluble compounds with various pharmacological and biological characteristics (antibacterial, antiswelling, antifungal, parkinson and etc.). They are used for treatment HIV and cancer. This study investigated the effects of 4(3H) quinazlonones-2-ethyl-2-phenyl ethyl (QEPE) as a new quinazolinons compounds on the spleen and immunocompetent cells of newborn Balb/C mice. Pregnant mice were divided into 3 groups (n=10) of control, sham and experimental, received distilled water, methyl cellulose %0.05 (the solvent) and 100 mg/kg body weight (ip) of QEPE (most effective dose), respectively, on days 8 to 15 of gestation. Examinations indicated an increase in weight of spleen in experimental group. Pathological studies showed increase in capsule thickness and number of macrophage cells of experimental group. Statistical analysis showed significant differences in morphological studies between experimental, sham and control groups. The statistical data on capsule thickness and number of macrophage cells indicated significant differences between groups. Detailed observations showed an increase in the volume of monocyte, neutrophile and eosinophile, in response to QEPE, but the volume of lymphocyte and basophile were similar in experimental, control and sham groups. The damages caused by this dose of QEPE could have been the reason for the increase in the number of immonucompetent and macrophage cells. Some studies showed damages to the organs such as livers and hearts would lead to the increase in the thickness of spleen capsule, consequently, increase in its weight and leading to splenomegaly. So, QEPE can not be an appropriate candidate for drug development. QEPE in lower doses might be an appropriate candidate for increase of immune system resistance.


Baek, D. J., T. B. Kang, and K. H. J. 2004.Synthesis of nonclassical quinazolinone antifolates as thymidylate synthase
inhibitors and their antitumor activity in vitro. B. Kor. Chem. Soc. . 25(12),1896-1906.
Bordmann, G., N. Favre, and W. Rudin. 1997.Malaria Toxin: Effects on murine spleen and bone marrow cell proliferation and
cytokine production in vitro. Parasitology.115,475-483.
Boumendjel, A., H. Baubichon-Cortay, D.Trompier, T. Perrotton, and A. Di Pietro.2005. Anticancer multidrug resistance
mediated by MRP1: recent advances in the discovery of reversal agents. . Med. Res.Rev. . 25(4),453-472.
Brecher, M., C. Harbaugh, and A. Pineda.1992. Accurate counting of low numbers of leukocytes: use of flow cytometry and
manual low-count chamber. J. Clin. Pathol.97,872-875.
Buyuktimkin, S., A. C. Ekinci, N.Buyuktimkin, and G. Otuk. 2006.
Pharmacological studies on quaternized 4(3H)-quinazolinones. J. Pharm. Sci.81(11),1092-1094.
Corbett, J. W., S. Ko, J. D. Rodgers, and S. K.Erickson. 2000. Inhibition of clinically relevant mutant variants of HIV-1 by
quinazolinone nonnucleoside reverse transcriptase inhibitors. . J. Med. Chem.43,2019-2030.
Dabiri, M., P. Salehi, M. S. Khajavi, and A.Mohammadi. 2004. Microw ae-assisted one-pot three component synthesis of some
new 4(3H)-quinazolinone derivatives.Heterocycles 63(6),1417-1421.
David, J., C. Declan, S. Timothy, and J.Patrick. 2005. Synthesis of quinazolinones and quazolines. Tetrahedron. 61(43),10153-
Etemad, S. and M. Shams Lahijani. 2007.Quinazolinones and nerphrotoxicity in new born Balb/C mice. 7th World Congress of
Nephrology (WCN), Rio de Janeiro, Brazil.
Fadavi, M. and M. Shams Lahijani. 2007.Pathological effects of quinazolinones on the small intestine of new born Balb/C
mouse. XI International Congress of Toxicology (ICT), Montreal, Canada.
Institoris, L., O. Siroki, U. Undeger, N.Basaran, B. D. Banerjee, and I. Desi. 2001.Detection of the effects of repeated dose
combined propoxur and heavy metal exposure by measurement of certain toxicological, haematological and immune function parameters in rats. Toxicology 163,185-193.
James, F. W., L. R. Terry, C. S. Mark, and F.W. Thomes. 1990. Synthesis and anticonvulsant activity of some new
substituted 3- aryl – 4(3) – quinazolinones.J. Med. Chem. 33,161-166.
Jatav, V., S. K. Jain, S. K. Kashaw, and P.Mishra. 2006. Synthesis and antimicrobial activity of novel 2-methyl-3-(1'3'4'-
Thiadiazoyl)-4-(3h) quinazolinones. Indian J. Pharmaceut. Sci. . 63(3),360-363.
Jennifer, A. B., A. V. Laura, B. Joel, H. Brain,and S. L. abine. 2004. Effect of heavy metals on immunocompetence of whitefooted mice (Peromyscus leucopus). . J.Wildl. Dis. 40(2),173-148.
Jimenez, V., D. P. Cardinal, M. P. Alvarez,and A. L. Boggiov. 2005. Effect of chronic ethanol feeding on 24-hour rhythms of
mitogenic responses and lymphocyte subset populations in spleen of peripubertal male rats. Neuroimmunomodulat. 12,357-365.
Keith, A. G. 2002. Assessing immunological function in toxicological studies of avian wildlife. Integr. Comp. Biol. . 42,34-42.
Mann, J., H. Li, L. Kuo, and C. Sheng. 2006.6-Alkylamino and 2,3 Dihydro-3- methoxy-2-phenyl-4-quinazolinones and related
compounds: Their synthesis, cytotoxicty and inhibition of tubulin polymerization. J.Med. Chem. 43(23),4479-4487.
Matsumoto, M., S. Aiso, H. Senoh, and T.Matsushima. 2006. Chronic toxicity of para-chloronitrobenzene in rats. Environ.
Pathol. Toxicol. Oncol. 25(3),571-575.
Ouyang, G., P. Zahng, G. Xu, B. Song, L. Jin,W. Xue, D. Hu, P. Lu, and Z. Chen. 2006.Synthesis and antifungal bioactivities of 3-
alkylquinazolin-4-one derivatives.Molecules 11:383-392.
Paula, M., B. B. William, and M. H. Wanda.1998. Preventation of T-2toxin-induced morphologic effects in the rat by highly
activated charcoal. Toxicology.117(11),459-464.
Perretti, L. and L. Zilletti. 1969.Transplacental of methyl-o-tolylquinazolinone in rat. . Riv. Stet. Ginecol. .
Pines, M., I. Vlodavsky, and A. Nagler. 2000.Halofuginone: from veterinary use to human therapy. . Drug Develop. Res. 50(3-
Radovan, B. 1987. Splenic fibrosis in patients with chronic schistosomiasis. Mem. Inst.Oswaldo Cruz, Rio de Janeiro 82,253-255.
Rajabi, H. and M. Shams Lahijani. 2007.Histological study of liver of newborn Balb/C mice treated with quinazolinones.
XI International Congress of Toxicology (ICT, Montreal, Canada.
Richard, A. J., J. K. Thomas, A. O. Barbara,and K. Janis. 1997. Immunology, New York.
Riddle, M. M., W. C. Williams, and R. J.Smialowicz. 1996. Methoxyacetic suppress humoral immunity in the mouse.
Toxicology. 109(1),67-74.
Sama, R. and P. Moro. 1993. NTP technical report on the toxicity studies of the Glycol Ethers: 2-methoxyethanol and 2-
ethoxyethanol. . J. Med. Chem. 16(23),479-487.
Sehu, A., L. Erqun, S. Cakir, and T. Sahin.2007. Hydrated sodium calcium aluminosilicate for reduction of alfatoxin in quails. Toxicology. 114(7),252-259.
Shams lahijani, M., F. Ahmadzadeh, and M.Dabiri. 2006. Teratogenic effects of new quinazolinone derivative on the
development of Balb/C mice fetuses on days 9, 10 and 11 of gestation. Iran. J. Sci.Technol. 30,1-8.
Shams lahijani, M. and A. R. 2007.Teratogenic effect of quinazolinone on Balb/C mice fetuses. JMSR. 1(1),25-30.
Wanless, I. R. and V. Bernier. 1983. Fibrous thickening of the splenic capsule. A response to chronic splenic congestion.
Arch. Pathol. Lab. Med. . 107(1),595-599.
Med. Chem. Lett. . 11,1193-1196.
Xia, Y., Z. Y. Yang, M. J. Hour, S. C. Kuo, P.Xia, K. F. Bastow, Y. Nakanishi, P.Nampoothiri, T. Hackl, E. Hamelc, and K.
H. Lee. 2001. Antitumor agents. Part 204.1: Synthesis and biological evaluation of substituted 2-aryl quinazolinones. Bioorg.
Yesilada, A., S. koyunoglu, N. Saygilia, E.Kupeli, E. Yesilida, E. Bedir, and I. Khanc.2004. Synthesis,anti inflammatory and
analgesic activity of some new4(3H)-quinazolinones derivatives. Archiv. Der.Pharmazie. 337(2),96-104.