Synthesis and biological evaluation of new 4-thiazolidinone derivatives

Figures & data

Scheme 1.  Reagents: (i) hydrazine hydrate, EtOH, reflux, 6 h; (ii) EtOH, reflux, 4 h; (iii) mercaptoacetic acid/2-mercaptopropionic acid, dry benzene, reflux, 6 h.

Table 1.  The primary in vitro antimycobacterial activity of compounds 3a-r and 4a-r were determined against M. tuberculosis H37Rv using Microplate Alamar Blue Assay (MABA). The compounds were tested at a concentration of 6.25 µg/mL. The inhibition values of the compounds with more than 90% growth inhibition are indicated in boldface.

Compound	R	R1	GI (%)^a
3a	2-F	H	28
3b	3-F	H	30
3c	4-F	H	9
3d	2-Cl	H	0
3e	3-Cl	H	0
3f	4-Cl	H	99
3g	2-Br	H	25
3h	3-Br	H	44
3i	4-Br	H	0
3j	2,4-Cl	H	0
3k	3,4-Cl	H	0
3l	2,6-Cl	H	0
3m	2-Cl-6-F	H	29
3n	4-CF3	H	0
3o	4-CN	H	98
3p	4-OCH2C6H5	H	98
3r	4-SCH3	H	15
4a	2-F	CH3	29
4b	3-F	CH3	27
4c	4-F	CH3	25
4d	2-Cl	CH3	95
4e	3-Cl	CH3	0
4f	4-Cl	CH3	99
4g	2-Br	CH3	28
4h	3-Br	CH3	36
4i	4-Br	CH3	0
4j	2,4-Cl	CH3	16
4k	3,4-Cl	CH3	0
4l	2,6-Cl	CH3	0
4m	2-Cl-6-F	CH3	34
4n	4-CF3	CH3	4
4o	4-CN	CH3	99
4p	4-OCH2C6H5	CH3	98
4r	4-SCH3	CH3	25

^aGrowth inhibition of virulent H37Rv strain of M. tuberculosis.

Table 2.  In vitro tumor cell growth inhibition of 4p.

Panel/cell line	4p		Panel/cell line	4p		Panel/cell line	4p		Panel/cell line	4p		Panel/cell line	4p
	log10GI50	log10TGI	log10GI50	log10TGI		log10GI50	log10TGI		log10GI50	log10TGI			log10GI50	log10TGI
Leukemia			Colon cancer			Melanoma			Renal cancer			Breast cancer
CCRF-CEM	−5.68	−5.24	COLO 205	−5.70	−5.37	LOX IMVI	−5.41	−4.84	786-O	−5.70	−5.33	MCF7	−5.36	−4.65
HL-60(TB)	−5.73	−5.30	HCC-2998	−5.72	−5.30	MALME-3M	−5.67	−4.98	A498	−5.48	−4.86	NCI/ADR-RES	−5.43	−4.75
K-562	−5.47	>4.00	HCT-116	−5.75	−5.33	SK-MEL-2	−5.36	−4.72	ACHN	−5.56	−5.03	MDA-MB	−5.37	−4.81
MOLT-4	−5.70	−4.06	HCT-15	−5.56	−4.89	SK-MEL-28	−5.35	−4.79	CAKI-1	−5.60	−5.07	231/ATCC	−5.71	−5.15
RPMI-8226	−5.69	−5.21	HT29	−5.52	−5.11	SK-MEL-5	−5.08	−4.68	SN12C	−5.40	−4.86	HS 578T	−5.45	−4.86
SR	−5.93	−5.48	KM12	−5.64	−5.20	UACC-257	−5.13	−4.67	TK-10	−5.59	−4.85	MDA-MB 435	−5.26	−4.65
			SW-620	−5.44	4.90	UACC-62	−5.43	−4.80	UO-31	−5.43	−4.67	BT-549 T-47D	−5.45	−4.83
Non-small cell lung cancer			CNS cancer			Ovarian cancer			Prostate cancer
A549/ATCC	−5.33	−4.68	SF-268	−5.44	−4.82	IGROV1	−5.62	−4.94	PC-3	−5.68	−5.16	MG MID	−5.48	−4.90
EKVX	−5.26	−4.65	SF-295	−5.75	−5.34	OVCAR-3	−5.63	−5.21	DU-145	−5.45	−4.87	Delta	0.46	0.58
HOP-62	−5.70	−5.09	SF-539	−4.86	−4.37	OVCAR-4	−5.29	−4.44					1.08	1.38
HOP-92	−5.94	−5.32	SNB-19	−5.30	−4.67	OVCAR-5	−5.42	−4.79				Range
NCI-H226	−5.42	−4.80	SNB-75	−5.43	−4.74	OVCAR-8	−5.90	−4.41
NCI-H23	−5.57	−4.86	U251	−5.39	−4.81	SK-OV-3	−5.02	−4.48
NCI-H322M	−5.32	−4.69
NCI-H460	−5.45	−4.89