Synthesis of mono Mannich bases of 2-(4-hydroxybenzylidene)-2,3-dihydroinden-1-one and evaluation of their cytotoxicities

Figures & data

Scheme 1. Synthesis of MT1.

Scheme 2. Synthesis of MT8–MT15.

Table 1. Cytotoxicities of the compounds and log P values.

	CC50 (µmol/L)
	Tumour cell lines										Non-malignant cells				PSE
Compound	Ca9-22 (A)	SI	HSC-2 (B)	SI	HSC-3 (C)	SI	HSC-4 (D)	SI	Mean ± SD (E)	SI (J)	HGF (F)	HPLF (G)	HPC (H)	Mean ± SD (I)	J/E ×100	Log p*
MT1	304	2.28	155	4.48	262	2.65	186	3.73	227 ± 68	3.28	789	540	754	694 ± 135	1.44	3.12
MT8	48	1.13	7.1	7.6	23	2.35	6.8	7.9	21 ± 19	4.75	55	46	62	54 ± 8.0	22.62	2.81
MT9	124	>3.85	61	>7.84	52	>9.19	178	>2.69	104 ± 59	>5.89	262	173	>1000	>478	5.66	2.66
MT10	>1000	<0.8	547	1.46	77	10.39	>1000	<0.8	>656	<3.36	806	705	888	800 ± 92	<0.51	3.79
MT11	55	4.05	104	2.14	32	6.97	104	2.14	74 ± 36	3.83	227	200	241	223 ± 21	5.17	3.37
MT12	121	1.59	92	2.09	105	1.83	81	2.37	100 ± 17	1.97	139	208	228	192 ± 47	1.97	3.06
MT13	187	1.66	142	2.18	101	3.07	170	1.82	150 ± 38	2.18	453	220	257	310 ± 125	1.45	3.74
MT14	88	7.84	68	10.15	84	8.21	89	7.75	82 ± 10	8.49	570	717	784	690 ± 109	10.35	4.71
MT15	>1000	>1	>1000	>1	>1000	>1	>1000	>1	>1000	>1	>1000	>1000	>1000	>1000	>0.1	6.52
Average	>325.22	>2.70	>241.78	>4.32	>192.8	>5.07	>312.75	>3.35	>268.22	>3.86	>477.88	>507.55	>579.33	>493.44	5.47
Melphalan	22.6	6.5	8.5	17.3	5.6	26.2	11.9	12.3	12.2 ± 7.4	15.6	140.0	179.0	123.0	147.0 ± 29.0	127.87
5-FU	29	>34.5	13	>76.9	16	>62.5	13	>76.9	18 ± 7.6	>62.7	>1000	>1000	>1000	>1000	348.33

In this table, the CC₅₀ values refer to the concentrations of the compounds in micromoles which kill 50% of the cells. The letters SI indicate the selectivity index, i.e. the quotient of the average CC₅₀ figures towards HGF, HPC and HPLF non-malignant cells divided by the CC₅₀ figure of the compound towards a specific tumour cell line. The letters PSE indicate the potency selectivity expression which is the product of the reciprocal of the average CC₅₀ figure towards Ca9–22, HSC-2, HSC-3 and HSC-4 cell lines and the average SI value towards these neoplasms expressed as a percentage. *Log P values were calculated using ChemDraw Ultra 12.0 software.