Chemopreventive potential of 3-[2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino]-2-thioxoimidazolidin-4-one on 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis

Figures & data

Scheme 1.  Synthetic rote for the formation of 3-(2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino)-2-thioxoimidazolidin-4-one

Scheme 2.  Proposed reaction mechanism for the formation of the title compound.

Table 1.  Body weight, tumour incidence, tumour multiplicity, tumour burden and incidence of preneoplastic and neoplastic lesions in control and experimental animals (mean ± SD; n = 6).

Group	Treatment	Body weight (g)		Tumour incidence	Tumour multiplicity No. of tumours/ Hamsters	Tumour Burden (mm^3)*	Keratosis	Hyperplasia	Dysplasia
		Initial	Final
1	DMBA	103 ± 9.21	115 ± 10^a	6/6	1.17 ± 0.41	208 ± 43.68	+++	+++	+++
2	DMBA + title compound (1mg/kg BW)	105 ± 8.34	125 ± 11	1/6^b	0.16 ± 0.4^b	5.55 ± 13.6^b	+++	+++	++/+++
3	DMBA + title compound (10mg/kg BW)	106 ± 10	126 ± 9	-	-	-	++	+/++	+
4	Control	110 ± 11	134 ± 11	-	-	-	++	++	+/++

+, mild; ++, moderate; +++, Severe; -, no change.

*Mean tumour burden was calculated by multiplying the mean tumour volume (4/3 πr³) with the mean number of tumours (r = 1/2 tumour diameter in mm).

^aSignificantly different from group 4 by student’s t test (p< 0.01).

^bSignificantly different from group 1 by λ² –test (p<0.001).

Table 2.  The cellular redox status in the buccal pouches of experimental and control animals (mean ± SD; n = 10).

Group	Treatment	TBARS (n mol/mg protein)	SOD (U^a/mg protein)	Catalase (U^b/mg protein)	GSH (mg/g tissue)	GPX (U^c/mg protein	GST (U^d/mg protein)
1	DMBA	4.6 ± 0.33	2.34 ± 0.21	1.18 ± 0.1	0.18 ± 0.01	10.65 ± 0.75	5.7 ± 0.43
2	DMBA+ TitleCompound (1mg/kg BW)	5.49 ± 0.38*	2.83 ± 0.25**	1.37 ± 0.12*	0.23 ± 0.02*	11.86 ± 1.31*	6.43 ± 0.56*
3	DMBA+ Titlecompound (10mg/kg BW)	5.74 ± 0.56**	4.3 ± 0.32***	1.54 ± 0.15***	0.25 ± 0.01***	12.53 ± 1.4**	6.92 ± 0.63***
4	Control	6 ± 0.92	5.01 ± 0.43	2.13 ± 0.21	0.13 ± 0.01	7.25 ± 0.51	3.98 ± 0.34

Significantly different from group 4 (p<0.001) ANOVA followed by LSD.

^* Significantly different from group 1 (p<0.05) ANOVA followed by LSD.

^** Significantly different from group 1 (p<0.01) ANOVA followed by LSD.

^*** Significantly different from group 1 (p<0.001) ANOVA followed by LSD.

^a The amount of enzyme required to inhibit 50% NBT reduction.

^b μmoles of H₂O₂ utilised/min.

^c μmoles of GSH utilised/min.

^d μmoles of 1-chloro-2,4-dinitrobenzene-reduced glutathione conjugate formed/min.