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European	Journal	of	Chemistry	5	(1)	(2014)	144‐149	

	

European	Journal	of	Chemistry	
ISSN	2153‐2249	(Print)	/	ISSN	2153‐2257	(Online)		2014	Eurjchem	Publishing	‐	Printed	in	the	USA	

http://dx.doi.org/10.5155/eurjchem.5.1.144‐149.925	

	
	

	

	

European	Journal	of	Chemistry	
Journal	homepage:	www.eurjchem.com	

	 	 	

Synthesis,	characterization	and	in	vitro	evaluation	of	some	new	5‐benzylidene‐
1,3‐thiazolidine‐2,4‐dione	analogs	as	new	class	of	α‐glucosidase	inhibitors	

Divakara	Laxman	Somayajulu	Nori	a,*,	Kasapu	Vishnu	Veera	Venkata	Satyanarayana	a,		
Vasudeva	Rao	Avupati	b,	Bharat	Kumar	Bugata	c	and	Subhash	Yenupuri	a	

a	Department	of	Chemistry,	Gitam	University,	Rushikonda,	Visakhapatnam‐530045,	Andhra	Pradesh,	India	
b	Pharmaceutical	Chemistry	Division,	Andhra	University	College	of	Pharmaceutical	Sciences,	Andhra	University,	Visakhapatnam‐530003,	Andhra	Pradesh,	India	
c	Department	of	Biochemistry	and	Bioinformatics,	Gitam	University,	Rushikonda,	Visakhapatnam‐530045,	Andhra	Pradesh,	India	

*Corresponding	author	at:	Department	of	Chemistry,	Gitam	University,	Rushikonda,	Visakhapatnam‐530045,	Andhra	Pradesh,	India.		
Tel.:	+91.0891.2792928.	Fax:	+91.0891.2790399.	E‐mail	address:	divakarsomu@gmail.com		(D.L.S.	Nori).	

	
	

	 	

	 	 	
ARTICLE	INFORMATION	 	 ABSTRACT	

	
DOI:	10.5155/eurjchem.5.1.144‐149.925	

Received:	10	September	2013	
Received	in	revised	form:	18	October	2013	
Accepted:	29	October	2013	
Online:	31	March	2014	

KEYWORDS	

	 A	series	of	5‐benzylidene‐1,3‐thiazolidine‐2,4‐dione	derivatives	(5a‐u)	were	synthesized	and
tested	against	α‐glucosidase.	Preparation	of	the	titled	compounds	was	achieved	by	reaction	of
(Z)‐4‐((2,4‐dioxo‐1,3‐thiazolidin‐5‐ylidene)methyl)benzaldehyde	 (4)	 and	 aromatic/hetero
aromatic	 ketone.	 Among	 the	 compounds	 tested,	 (5p)	 and	 (5o)	were	 identified	 as	 the	most
active	 in	 vitro	 with	 minimum	 inhibitory	 concentration	 (MIC)	 of	 6.56±0.81	 and	 8.92±0.21
µg/mL	against	α‐glucosidase,	respectively.	Evaluation	of	the	structure	activity	relationship	of
substituents	within	these	series	has	followed	the	discovery	of	a	variety	of	compounds.	

α‐Glucosidase	
Structure	activity	relationship	
Aromatic/heteroaromatic	ketone	
Thiazolidine‐2,4‐dione	derivatives		
Minimum	inhibitory	concentration	
5‐Benzylidene‐1,3‐thiazolidine‐2,4‐dione	

	
1.	Introduction	
	

α‐Glucosidases	(α‐D‐glucoside	glucohydrolase	E.C.	3.2.1.20)	
are	 membrane	 bound	 exo‐acting	 enzymes,	 located	 at	 the	
epithelium	of	 the	 small	 intestine	 [1].	They	are	 responsible	 for	
catalyzing	 the	 final	 step	 in	 the	 digestive	 process	 of	
carbohydrate	metabolism.	α‐Glucosidases	are	the	key	enzymes	
that	 hydrolyze	O‐	 and	 S‐glycosyl	 residues,	 are	 involved	 in	 the	
biosynthesis	 and	 processing	 of	 oligosaccharide	 chains	 of	 N‐
linked	glycoproteins	in	the	endoplasmic	reticulum	(ER)	[2].	The	
most	 extensively	 studied	 are	 α	 and	 β‐glucosidases	 that	 are	
known	to	catalyze	the	hydrolysis	of	glycosidic	bonds	involving	
a	 terminal	 glucose	 at	 the	 cleavage	 site	 through	 α‐	 and	 β‐
linkages	 at	 the	 anomeric	 centre	 [3].	 These	 two	 glucosidases	
differ	 in	how	 to	position	 their	 two	carboxylic	acid	 side	chains	
during	 catalysis,	 one	 plays	 the	 role	 of	 a	 catalytic	 nucleophile	
attacking	 the	 anomeric	 centre,	 and	 the	 other	 acts	 as	 an	 acid	
catalyst	weakening	the	C‐O	bond	by	protonation.	Between	the	
two	 popular	 glucosidases,	 α‐glucosidase	 has	 drawn	 a	 special	
interest	 of	 the	 medicinal	 chemists	 because	 it	 was	 shown	 in	
earlier	studies	that	inhibition	of	its	catalytic	activity	resulted	in	
the	retardation	of	glucose	absorption	and	the	decrease	in	post	
prandial	 blood	 glucose	 level	 [4].	 Several	 sugar	 α‐glucosidase	

inhibitors,	 including	 acarbose,	 voglibose	 and	 miglitol	 are	
clinically	 used	 in	 the	 effective	 treatment	 of	 type‐2	 diabetes	
mellitus.	 However,	 such	 inhibitors,	 which	 are	 of	 great	
structural	 diversity,	 require	 tedious	 multisteps	 during	
preparation	 [5].	 Hence,	 greater	 attention	 is	 focused	 on	 non‐
sugar	 α‐glucosidase	 inhibitors	 [6].	 The	 design	 of	 glucosidase	
inhibitors	with	a	high	degree	of	specificity	and	potency	 is	still	
needed	 for	 exploration	 of	 new	 inhibitors	 [7].	 α‐Glucosidase	
inhibitors	are	also	known	to	be	promising	as	antiviral,	anti‐HIV	
agents,	 which	 alter	 glycosidation	 of	 envelop	 glycoprotein	
through	 interference	 with	 biosynthesis	 of	 N‐linked	
oligosaccharides	 [8].	 Recently,	 several	 synthetic	 ligands	 have	
been	reported	to	inhibit	α‐Glucosidase	[9,10].	

Thiazolidinediones	 (TZDs)	 are	 the	 derivatives	 of	
thiazolidine,	 which	 belongs	 to	 an	 important	 group	 of	 five‐
membered	 biologically	 active	 heterocyclic	 compounds.	
Thiazolidinediones	 have	 an	 atom	 of	 sulfur	 at	 position	 1,	 an	
atom	 of	 nitrogen	 at	 position	 3	 and	 two	 carbonyl	 groups	 each	
one	 at	 ‐2,	 ‐4	 or	 ‐2,	 ‐5	 or	 ‐4,	 ‐5	positions,	 respectively	 [11].	 In	
terms	of	 their	 chemistry,	different	possibilities	of	heterocyclic	
modifications	 with	 a	 wide	 spectrum	 of	 pharmacological	
properties	are	the	most	important	grounds	for	investigations	of	
this	interesting	class	of	compounds	[12].		



Nori	et	al.	/	European	Journal	of	Chemistry	5	(1)	(2014)	144‐149	 145	
 

	

	
	

Scheme	1	
	
	
The	 positions	 3	 (‐NH‐	 group)	 and	 5	 (‐CH2‐	 group)	 on	 the	

TZD	 ring	 are	 relatively	 more	 reactive;	 hence,	 most	 of	 the	
modifications	 on	 the	TZD	 ring	 are	 done	 on	 these	positions	 to	
synthesize	new	molecules	[13].	Primarily,	2,4‐thiazolidinedione	
(3)	 scaffold	 is	 extremely	 versatile	 and	 its	 derivatives,	 also	
referred	 as	 glitazones,	 represent	 the	most	 promising	 class	 of	
compounds	having	 a	wide	 variety	 of	 biological	 activities	 [14].	
TZDs	 are	 a	 class	 of	 insulin	 sensitizing	 drugs,	 which	 include	
ciglitazone,	 pioglitazone,	 troglitazone	 and	 rosiglitazone	 [15].	
TZDs	are	known	 to	 stimulate	PPAR‐γ	receptor,	 they	also	have	
multiple	 PPAR‐γ	 independent	 biological	 profiles,	 such	 as	
antimalarial	 [16],	 antioxidant	 [17],	 antitumor	 [18],	 cytotoxic	
[19],	 anti‐inflammatory	 [20],	 antimicrobial	 [21],	 radical	
scavenger	 [22],	 glycogen	 synthase	 kinase	 (GSK)	 3	 inhibitor	
[23],	 chymase	 inhibitor	 [24],	 aldose	 reductase	 inhibitor	 [25],	
cholesterol	 esterase	 inhibitor	 [26],	 thyroid	 hormone	 receptor	
antagonist	[27]	and	neuroprotective	[28].		

As	 a	 part	 of	 our	 ongoing	 research	 in	 systematic	
investigation	of	synthesizing	some	novel	bioactive	compounds	
in	 relation	 to	 their	 α‐glucosidase	 inhibitory	 activity,	 we	
prepared	 various	 5‐benzylidene‐1,3‐thiazolidine‐2,4‐diones	
(5a‐u).	 However,	 we	 have	 found	 that	 5‐benzylidene‐1,3‐
thiazolidine‐2,4‐diones	 (5a‐u)	have	 the	considerable	potential	
to	act	as	a	new	class	of	α‐glucosidase	 inhibitors,	which	can	be	
obtained	 with	 the	 efficient	 methods	 in	 organic	 synthesis	
(Scheme	 1).	 The	 novelty	 of	 this	 work	 is	 that	 none	 of	 the	 5‐
benzylidene‐1,3‐thiazolidine‐2,4‐diones	 (5a‐u)	 synthesized	 in	
the	 present	 study	 were	 earlier	 not	 reported	 to	 possess	 any	
inhibitory	activity	against	α‐glucosidase	enzyme.	
	
2.	Experimental	 	
	
2.1.	Instrumentation	

	
Melting	points	were	 taken	 in	open	capillary	 tubes	and	are	

therefore	 uncorrected.	 Purity	 of	 the	 compounds	was	 checked	
on	silica	gel	G	TLC	plates	of	2	mm	thickness	using	n‐hexane	and	
ethyl	 acetate	 as	 solvent	 system.	The	 visualization	 of	 spot	was	
carried	 out	 in	 an	 iodine	 chamber.	 The	 FT‐IR	 spectra	 were	
recorded	 on	Perkin‐Elmer	 spectrometer.	 The	 1H	NMR	 spectra	
were	scanned	on	a	Bruker	400	MHz	spectrometer	 in	DMSO‐d6	
using	 TMS	 as	 internal	 standard	 and	 chemical	 shifts	 are	
expressed	in	δ	ppm.	The	Electronspray	Ionisation	mass	spectra	
(ESI‐MS)	 were	 recorded	 on	 an	 Agilent	 6100	 QQQ	 mass	
spectrometer	 (positive	 ion	 mode).	 The	 UV‐Vis	 absorption	
spectra	of	 the	compounds	were	recorded	on	a	Hitachi	U‐1600	
spectrophotometer.		

	

2.2.	 General	 procedure	 for	 the	 synthesis	 of	 5‐benzylidene‐
1,3‐thiazolidine‐2,4‐diones	(5a‐u)	
	

The	reaction	sequence	intended	for	the	preparation	of	title	
compounds	 (5a‐u)	 is	 shown	 in	 Scheme	 1,	 and	 their	 physical	
properties	 are	 depicted	 in	 Table	 1.	 The	 chief	 intermediate	 in	
the	 present	 study	 (Z)‐4‐((2,4‐dioxo‐1,3‐thiazolidin‐5‐ylidene)	
methyl)benzaldehyde	 (4)	 was	 prepared	 by	 Knoevenagel	
condensation	 reaction	 between	 terephthalaldehyde	 and	 1,3‐
thiazolidine‐2,4‐dione.	 Further,	 successive	 base	 catalyzed	
condensation	of	the	(4)	with	appropriate	substituted	aromatic/	
heteroaromatic	 ketones	 in	 the	 presence	 of	 100%	 potassium	
hydroxide	 solution	 in	 ethanol	 afforded	 a	 series	 of																									
5‐benzylidene‐1,3‐thiazolidine‐2,4‐diones	(5a‐u)	in	good	yield.	
All	 the	 newly	 synthesized	 compounds	 were	 characterized	 by	
CHN	elemental	analysis	and	spectroscopic	methods	such	as	FT‐
IR,	 1H	NMR,	 and	 LC	mass	 spectral	 analysis.	 Eventually	 all	 the	
spectra	 of	 the	 new	 products	 (5a‐u)	 are	 in	 keeping	 with	 the	
predictable	structures	[29].		

(Z)‐5‐(4‐((E)‐3‐(2‐methylphenyl)‐3‐oxoprop‐1‐enyl)benzyli	
dene)‐1,3‐thiazolidine‐2,4‐dione	 (5a):	 Colour:	 Yellow.	 Yield:	
79%.	 M.p.:	 137‐139	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3155	 (N−H),	
3031	(C−H,	aromatic),	2884	(C−H,	aliphatic),	1688	(C=O),	1645	
(C=C,	aliphatic),	1513	(C=C,	aromatic),	689	(C−S).	1H	NMR	(400	
MHz,	DMSO‐d6,	δ,	ppm):	2.32	(s,	3H,	CH3),	7.43‐8.04	(m,	8H,	Ar‐
H),	7.78	(d,	 J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.98	(s,	1H,	HC=C),	
8.01	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	12.74	(s,	1H,	NH).	ESI‐
MS	(m/z):	350	[M+H]+.	Anal.	calcd.	for	C20H15NO3S:	C,	68.75;	H,	
4.33;	N,	4.01.	Found:	C,	67.91;	H,	4.34;	N,	4.12%.	

(Z)‐5‐(4‐((E)‐3‐(3‐methylphenyl)‐3‐oxoprop‐1‐enyl)benzyli	
dene)‐1,3‐thiazolidine‐2,4‐dione	 (5b):	 Colour:	 Yellow.	 Yield:	
88%.	 M.p.:	 168‐170	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3127	 (N−H),	
3027	(C−H,	aromatic),	2777	(C−H,	aliphatic),	1703	(C=O),	1603	
(C=C,	aliphatic),	1450	(C=C,	aromatic),	688	(C−S).	1H	NMR	(400	
MHz,	DMSO‐d6,	δ,	ppm):	2.41	(s,	3H,	CH3),	7.38‐8.05	(m,	8H,	Ar‐
H),	7.73	(d,	 J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.98	(s,	1H,	HC=C),	
8.04	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	12.69	(s,	1H,	NH).	ESI‐
MS	(m/z):	350	[M+H]+.	Anal.	calcd.	for	C20H15NO3S:	C,	68.75;	H,	
4.33;	N,	4.01.	Found:	C,	68.73;	H,	4.31;	N,	4.11%.	

(Z)‐5‐(4‐((E)‐3‐(2‐methoxyphenyl)‐3‐oxoprop‐1‐enyl)benzyli	
dene)‐1,3‐thiazolidine‐2,4‐dione	 (5c):	 Colour:	 Yellow.	 Yield:	
91%.	 M.p.:	 238‐240	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3124	 (N−H),	
3027	(C−H,	aromatic),	2975	(C−H,	aliphatic),	1700	(C=O),	1603	
(C=C,	 aliphatic),	 1417	 (C=C,	 aromatic),	 713	 (C−S),	 1171	
(C−O−C),	 1054	 (C−O).	 1H	 NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	
3.86	(s,	3H,	OCH3),	7.20‐8.05	(m,	8H,	Ar‐H),	7.48	(d,	J	=	15.2	Hz,	
1H,	HC=CH	(H‐α)),	7.99	(s,	1H,	HC=C),	8.05	(d,	J	=	15.2	Hz,	1H,	
HC=CH	 (H‐β)),	 12.66	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 366	 [M+H]+.	



146	 Nori	et	al.	/	European	Journal	of	Chemistry	5	(1)	(2014)	144‐149	
	
Anal.	calcd.	for	C20H15NO4S:	C,	65.74;	H,	4.14;	N,	3.83.	Found:	C,	
65.79;	H,	4.17;	N,	3.88%.	

(Z)‐5‐(4‐((E)‐3‐(3‐methoxyphenyl)‐3‐oxoprop‐1‐enyl)benzyli	
dene)‐1,3‐thiazolidine‐2,4‐dione	 (5d):	 Colour:	 Yellow.	 Yield:	
78%.	 M.p.:	 181‐183	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3124	 (N−H),	
3027	(C−H,	aromatic),	2977	(C−H,	aliphatic),	1700	(C=O),	1605	
(C=C,	 aliphatic),	 1457	 (C=C,	 aromatic),	 687	 (C−S),	 1171	
(C−O−C),	 1054	 (C−O).	 1H	 NMR	 (400	MHz,	 DMSO‐d6,	 δ,	 ppm):	
3.88	(s,	3H,	OCH3),	7.12‐8.21	(m,	8H,	Ar‐H),	7.71	(d,	J	=	15.2	Hz,	
1H,	HC=CH	(H‐α)),	7.94	(s,	1H,	HC=C),	8.06	(d,	J	=	15.2	Hz,	1H,	
HC=CH	 (H‐β)),	 12.65	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 366	 [M+H]+.	
Anal.	calcd.	for	C20H15NO4S:	C,	65.74;	H,	4.14;	N,	3.83.	Found:	C,	
65.72;	H,	4.19;	N,	3.73%.	

(Z)‐5‐(4‐((E)‐3‐(3‐hydroxyphenyl)‐3‐oxoprop‐1‐enyl)benzyli	
dene)‐1,3‐thiazolidine‐2,4‐dione	 (5e):	 Colour:	 Yellow.	 Yield:	
77%.	 M.p.:	 179‐181	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3445	 (O−H),	
3124	(N−H),	3015	(C−H,	aromatic),	2984	(C−H,	aliphatic),	1689	
(C=O),	1606	(C=C,	aliphatic),	1415	(C=C,	aromatic),	676	(C−S),	
1054	 (C−O).	 1H	NMR	 (400	MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.36‐8.01	
(m,	8H,	Ar‐H),	7.67	(d,	 J	=	15.6	Hz,	1H,	HC=CH	(H‐α)),	8.01	(s,	
1H,	HC=C),	8.18	(d,	J	=	15.6	Hz,	1H,	HC=CH	(H‐β)),	12.32	(s,	1H,	
OH),	12.85	(s,	1H,	NH).	ESI‐MS	(m/z):	352	[M+H]+.	Anal.	calcd.	
for	 C19H13NO4S:	 C,	 64.95,	 H,	 3.73,	 N,	 3.99.	 Found:	 C,	 64.99,	 H,	
3.71,	N,	3.94%.	

(Z)‐5‐(4‐((E)‐3‐(3,5‐dihydroxyphenyl)‐3‐oxoprop‐1‐enyl)	
benzylidene)‐1,3‐thiazolidine‐2,4‐dione	 (5f):	 Colour:	 Yellow.	
Yield:	 85%.	 M.p.:	 224‐226	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3440	
(O−H),	 3122	 (N−H),	 3027	 (C−H,	 aromatic),	 2890	 (C−H,	
aliphatic),	 1700	 (C=O),	 1605	 (C=C,	 aliphatic),	 1511	 (C=C,	
aromatic),	688	(C−S),	1054	(C−O).	1H	NMR	(400	MHz,	DMSO‐d6,	
δ,	 ppm):	 7.21‐8.02	 (m,	 7H,	 Ar‐H),	 7.79	 (d,	 J	 =	 15.3	 Hz,	 1H,	
HC=CH	 (H‐α)),	 7.95	 (s,	 1H,	 HC=C),	 8.03	 (d,	 J	 =	 15.3	 Hz,	 1H,	
HC=CH	 (H‐β)),	 11.52	 (s,	 2H,	 OH),	 12.89	 (s,	 1H,	 NH).	 ESI‐MS	
(m/z):	 368	 [M+H]+.	 Anal.	 calcd.	 for	 C19H13NO5S:	 C,	 62.12;	 H,	
3.57;	N,	3.81.	Found:	C,	62.19;	H,	3.52;	N,	3.82%.	

(Z)‐5‐(4‐((E)‐3‐(4,5‐dihydroxyphenyl)‐3‐oxoprop‐1‐enyl)	
benzylidene)‐1,3‐thiazolidine‐2,4‐dione	 (5g):	 Colour:	 Yellow.	
Yield:	 84%.	 M.p.:	 219‐221	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3395	
(O−H),	 3127	 (N−H),	 3017	 (C−H,	 aromatic),	 2989	 (C−H,	
aliphatic),	 1686	 (C=O),	 1615	 (C=C,	 aliphatic),	 1545	 (C=C,	
aromatic),	689	(C−S),	1054	(C−O).	1H	NMR	(400	MHz,	DMSO‐d6,	
δ,	 ppm):	 7.55‐8.03	 (m,	 7H,	 Ar‐H),	 7.83	 (d,	 J	 =	 15.3	 Hz,	 1H,	
HC=CH	 (H‐α)),	 7.95	 (s,	 1H,	 HC=C),	 8.08	 (d,	 J	 =	 15.3	 Hz,	 1H,	
HC=CH	(H‐β)),	9.58	(s,	1H,	OH),	10.57	(s,	1H,	OH),	12.87	(s,	1H,	
NH).	ESI‐MS	(m/z):	368	[M+H]+.	Anal.	calcd.	for	C19H13NO5S:	C,	
62.12;	H,	3.57;	N,	3.81.	Found:	C,	62.17;	H,	3.59;	N,	3.89%.	

(Z)‐5‐(4‐((E)‐3‐(2‐methyl‐5‐hydroxyphenyl)‐3‐oxoprop‐1‐
enyl)benzylidene)‐1,3‐thiazolidine‐2,4‐dione	 (5h):	 Colour:	
Yellow.	 Yield:	 85%.	 M.p.:	 185‐187	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	
3440	 (O−H),	 3122	 (N−H),	 3021	 (C−H,	 aromatic),	 2975	 (C−H,	
aliphatic),	 1690	 (C=O),	 1641	 (C=C,	 aliphatic),	 1486	 (C=C,	
aromatic),	678	(C−S),	1054	(C−O).	1H	NMR	(400	MHz,	DMSO‐d6,	
δ,	ppm):	2.47	(s,	3H,	CH3),	7.62‐8.01	(m,	7H,	Ar‐H),	7.81	(d,	J	=	
15.3	Hz,	1H,	HC=CH	(H‐α)),	7.99	(s,	1H,	HC=C),	8.08	(d,	J	=	15.3	
Hz,	1H,	HC=CH	(H‐β)),	10.52	(s,	1H,	OH),	13.01	(s,	1H,	NH).	ESI‐
MS	(m/z):	366	[M+H]+.	Anal.	calcd.	for	C20H15NO4S:	C,	65.74;	H,	
4.14;	N,	3.83.	Found:	C,	65.72;	H,	4.19;	N,	3.86%.	

(Z)‐5‐(4‐((E)‐3‐(2‐aminophenyl)‐3‐oxoprop‐1‐enyl)benzyli	
dene)‐1,3‐thiazolidine‐2,4‐dione	 (5i):	 Colour:	 Yellow.	 Yield:	
83%.	 M.p.:	 241‐243	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3367	 (NH2),	
3117	(N−H),	2978	(C−H,	aromatic),	2763	(C−H,	aliphatic),	1693	
(C=O),	1597	(C=C,	aliphatic),	1413	(C=C,	aromatic),	688	(C−S),	
1296	 (C−N).	 1H	NMR	 (400	MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.74‐8.11	
(m,	8H,	Ar‐H),	7.58	(d,	 J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.95	(s,	
1H,	HC=C),	8.06	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	10.51	(s,	2H,	
Ar‐NH2),	 12.65	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 351	 [M+H]+.	 Anal.	
calcd.	 for	 C19H14N2O3S:	 C,	 65.13;	 H,	 4.03;	 N,	 7.99.	 Found:	 C,	
65.15;	H,	4.07;	N,	7.91%.	

(Z)‐5‐(4‐((E)‐3‐(3‐aminophenyl)‐3‐oxoprop‐1‐enyl)benzyli	
dene)‐1,3‐thiazolidine‐2,4‐dione	 (5j):	 Colour:	 Yellow.	 Yield:	
81%.	 M.p.:	 257‐259	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3367	 (NH2),	

3117	(N−H),	2978	(C−H,	aromatic),	2763	(C−H,	aliphatic),	1693	
(C=O),	1597	(C=C,	aliphatic),	1413	(C=C,	aromatic),	688	(C−S),	
1290	(C−N).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	7.72	(d,	J	=	
15.2	Hz,	1H,	HC=CH	(H‐α)),	7.74‐8.11	(m,	8H,	Ar‐H),	7.94	(s,	1H,	
HC=C),	8.01	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	10.54	(s,	2H,	Ar‐
NH2),	12.67	(s,	1H,	NH).	ESI‐MS	(m/z):	351	[M+H]+.	Anal.	calcd.	
for	C19H14N2O3S:	C,	65.13;	H,	4.03;	N,	7.99.	Found:	C,	65.11;	H,	
4.13;	N,	7.89%.	

(Z)‐5‐(4‐((E)‐3‐(2‐nitrophenyl)‐3‐oxoprop‐1‐enyl)benzylide	
ne)‐1,3‐thiazolidine‐2,4‐dione	 (5k):	Colour:	Yellow.	Yield:	84%.	
M.p.:	 247‐249	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3122	 (N−H),	 3024	
(C−H,	aromatic),	2776	(C−H,	aliphatic),	1700	(C=O),	1604	(C=C,	
aliphatic),	1414	(C=C,	aromatic),	688	(C−S),	1529	(N=O),	1291	
(C−N).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	6.86‐8.18	(m,	8H,	
Ar‐H),	 8.05	 (d,	 J	 =	 15.2	 Hz,	 1H,	 HC=CH	 (H‐α)),	 7.98	 (s,	 1H,	
HC=C),	8.35	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	12.72	(s,	1H,	NH).	
ESI‐MS	 (m/z):	 381	 [M+H]+.	 Anal.	 calcd.	 for	 C19H12N2O5S:	 C,	
59.99;	H,	3.18;	N,	7.36.	Found:	C,	59.92;	H,	3.15;	N,	7.16%.	

(Z)‐5‐(4‐((E)‐3‐(3‐nitrophenyl)‐3‐oxoprop‐1‐enyl)benzylide	
ne)‐1,3‐thiazolidine‐2,4‐dione	 (5l):	 Colour:	 Yellow.	 Yield:	 87%.	
M.p.:	 178‐180	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3115	 (N−H),	 3026	
(C−H,	aromatic),	2775	(C−H,	aliphatic),	1700	(C=O),	1599	(C=C,	
aliphatic),	1412	(C=C,	aromatic),	688	(C−S),	1522	(N=O),	1290	
(C−N).	1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	7.55‐8.39	(m,	8H,	
Ar‐H),	 7.86	 (d,	 J	 =	 15.2	 Hz,	 1H,	 HC=CH	 (H‐α)),	 7.98	 (s,	 1H,	
HC=C),	8.06	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐β)),	12.73	(s,	1H,	NH).	
ESI‐MS	 (m/z):	 381	 [M+H]+.	 Anal.	 calcd.	 for	 C19H12N2O5S:	 C,	
59.99;	H,	3.18;	N,	7.36.	Found:	C,	59.91;	H,	3.14;	N,	7.33%.	

(Z)‐5‐(4‐((E)‐3‐(2‐chlorophenyl)‐3‐oxoprop‐1‐enyl)benzylide	
ne)‐1,3‐thiazolidine‐2,4‐dione	(5m):	Colour:	Yellow.	Yield:	95%.	
M.p.:	 194‐196	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3127	 (N−H),	 3027	
(C−H,	aromatic),	2893	(C−H,	aliphatic),	1689	(C=O),	1597	(C=C,	
aliphatic),	1450	(C=C,	aromatic),	688	(C−S),	786	(C−Cl).	1H	NMR	
(400	MHz,	DMSO‐d6,	 δ,	ppm):	7.60	 (d,	 J	 =	15.2	Hz,	1H,	HC=CH	
(H‐α)),	7.62‐8.24	(m,	8H,	Ar‐H),	7.78	(d,	J	=	15.2	Hz,	1H,	HC=CH	
(H‐β)),	7.88	(s,	1H,	HC=C),	12.65	(s,	1H,	NH).	ESI‐MS	(m/z):	370	
[M+H]+.	Anal.	calcd.	for	C19H12ClNO3S:	C,	61.71;	H,	3.27;	N,	3.79.	
Found:	C,	61.74;	H,	3.22;	N,	3.77%.	

(Z)‐5‐(4‐((E)‐3‐(2,4‐dichlorophenyl)‐3‐oxoprop‐1‐enyl)benzy	
lidene)‐1,3‐thiazolidine‐2,4‐dione	 (5n):	 Colour:	 Yellow.	 Yield:	
92%.	 M.p.:	 227‐229	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3124	 (N−H),	
3018	(C−H,	aromatic),	2891	(C−H,	aliphatic),	1689	(C=O),	1641	
(C=C,	 aliphatic),	 1485	 (C=C,	 aromatic),	 691	 (C−S),	 786	 (C−Cl).	
1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	7.65‐8.23	(m,	7H,	Ar‐H),	
7.78	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.95	(s,	1H,	HC=C),	8.06	
(d,	 J	 =	 15.2	 Hz,	 1H,	 HC=CH	 (H‐β)),	 12.69	 (s,	 1H,	 NH).	 ESI‐MS	
(m/z):	405	[M+H]+.	Anal.	 calcd.	 for	C19H11Cl2NO3S:	C,	56.45;	H,	
2.74;	N,	3.46.	Found:	C,	56.23;	H,	2.71;	N,	3.42%.	

(Z)‐5‐(4‐((E)‐3‐(2‐fluorophenyl)‐3‐oxoprop‐1‐enyl)benzylide	
ne)‐1,3‐thiazolidine‐2,4‐dione	 (5o):	Colour:	Yellow.	Yield:	97%.	
M.p.:	 226‐228	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3117	 (N−H),	 3017	
(C−H,	aromatic),	2977	(C−H,	aliphatic),	1693	(C=O),	1605	(C=C,	
aliphatic),	 1415	 (C=C,	 aromatic),	 688	 (C−S),	 1116	 (C−F).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 7.36‐8.03	 (m,	 8H,	 Ar‐H),	
7.55	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.97	(s,	1H,	HC=C),	7.82	
(d,	 J	 =	 15.2	 Hz,	 1H,	 HC=CH	 (H‐β)),	 12.68	 (s,	 1H,	 NH).	 ESI‐MS	
(m/z):	 354	 [M+H]+.	 Anal.	 calcd.	 for	 C19H12FNO3S:	 C,	 64.58;	 H,	
3.42;	N,	3.96.	Found:	C,	64.55;	H,	3.41;	N,	3.99%.	

(Z)‐5‐(4‐((E)‐3‐(2,4‐difluorophenyl)‐3‐oxoprop‐1‐enyl)benzy	
lidene)‐1,3‐thiazolidine‐2,4‐dione	 (5p):	 Colour:	 Yellow.	 Yield:	
84%.	 M.p.:	 189‐191	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3122	 (N−H),	
3021	(C−H,	aromatic),	2884	(C−H,	aliphatic),	1693	(C=O),	1605	
(C=C,	aliphatic),	1415	(C=C,	aromatic),	688	 (C−S),	1114	(C−F).	
1H	NMR	(400	MHz,	DMSO‐d6,	δ,	ppm):	7.39‐8.31	(m,	7H,	Ar‐H),	
7.76	(d,	J	=	15.2	Hz,	1H,	HC=CH	(H‐α)),	7.94	(s,	1H,	HC=C),	8.08	
(d,	 J	 =	 15.2	 Hz,	 1H,	 HC=CH	 (H‐β)),	 12.69	 (s,	 1H,	 NH).	 ESI‐MS	
(m/z):	 372	 [M+H]+.	 Anal.	 calcd.	 for	 C19H11F2NO3S:	 C,	 61.45;	H,	
2.99;	N,	3.77.	Found:	C,	61.43;	H,	2.95;	N,	3.76%.	

(Z)‐5‐(4‐((E)‐3‐(furan‐2‐yl)‐3‐oxoprop‐1‐enyl)benzylidene)‐
1,3‐thiazolidine‐2,4‐dione	(5q):	Colour:	Yellow.	Yield:	93%.	M.p.:	
231‐233	oC.		



Nori	et	al.	/	European	Journal	of	Chemistry	5	(1)	(2014)	144‐149	 147	
 

	
Table	1.	Physical	characterization	and	α‐glucosidase	inhibitory	activity	data	of	5‐benzylidene‐1,3‐thiazolidine‐2,4‐diones	(5a‐5u).	
Compound	 R	 Yield	a	(%)	 Molecular	weight	(g)	 Molecular	formula	 M.p.	(oC)	 IC50	(µg/mL)	(mean±SEM)	c	
5a	 2‐MeC6H4	 79	 349	 C20H15NO3S 137‐139 33.06±0.25	
5b	 3‐MeC6H4	 88	 349	 C20H15NO3S 168‐170 15.28±0.15	
5c	 2‐OMeC6H4	 91	 365	 C20H15NO4S 238‐240 38.42±0.52	
5d	 3‐OMeC6H4	 78	 365	 C20H15NO4S 181‐183 49.17±0.14	
5e	 3‐OHC6H4	 77	 351	 C19H13NO4S	 179‐181	 29.82±0.12	
5f	 3,5‐diOHC6H3	 85	 367	 C19H13NO5S	 224‐226	 23.16±0.27	
5g	 4,5‐diOHC6H3	 84	 367	 C19H13NO5S 219‐221 19.20±0.37	
5h	 2‐Me,5‐OHC6H3	 85	 365	 C20H15NO4S	 185‐187	 29.82±0.12	
5i	 2‐NH2C6H4	 83	 350	 C19H14N2O3S	 241‐243	 27.03±0.11	
5j	 3‐NH2C6H4	 81	 350	 C19H14N2O3S 211‐213 38.42±0.52	
5k	 2‐NO2C6H4	 84	 380	 C19H12N2O5S 247‐249 39.77±0.23	
5l	 3‐NO2C6H4	 87	 380	 C19H12N2O5S 255‐257 41.82±0.14	
5m	 2‐ClC6H4	 95	 369	 C19H12ClNO3S 194‐196 32.11±0.33	
5n	 2,4‐diClC6H3	 92	 404	 C19H11Cl2NO3S 227‐229 29.47±0.32	
5o	 2‐FC6H4	 97	 353	 C19H12FNO3S	 226‐228	 8.92±0.21	
5p	 2,4‐diFC6H3	 84	 371	 C19H11F2NO3S 189‐191 6.56±0.81	
5q	 Furan‐2yl		 93	 325	 C17H11NO4S	 231‐233	 46.41±0.23	
5r	 Thiophen‐3‐yl	 82	 341	 C17H11NO3S2	 204‐206	 48.66±0.31	
5s	 Pyrrol‐2yl	 85	 324	 C17H12N2O3S	 191‐193	 30.84±0.66	
5t	 Pyridin‐4‐yl	 83	 336	 C18H12N2O3S 201‐203 37.39±0.26	
5u	 Naphthalen‐3‐yl	 87	 385	 C23H15NO3S 211‐213 33.12±0.64	
Standard	b	 ‐	 ‐	 ‐	 ‐ ‐ 0.007±0.27	
a	Crystallization	solvent	is	ethanol.	
b	Acarbose.	
c	SEM	=	Standard	error	of	the	mean.	
	
	

FT‐IR	(KBr,	vmax,	cm‐1):	3420	(N−H),	3062	(C−H,	aromatic),	
3030	 (C−H,	aliphatic),	1671(C=O),	1591	 (C=C,	 aliphatic),	1453	
(C=C,	aromatic),	696	(C−S),	1155	(C−O−C),	1053	(C−O).	1H	NMR	
(400	MHz,	DMSO‐d6,	 δ,	 ppm):	 6.74	 (s,	 1H,	Ar‐H),	 6.21	 (m,	 1H,	
Ar‐H),	7.16‐7.50	 (m,	5H,	Ar‐H),	7.62	 (d,	 J	 =	16	Hz,	1H,	HC=CH	
(H‐α)),	7.97	(s,	1H,	HC=C),	8.06	(d,	J	=	16	Hz,	1H,	HC=CH	(H‐β)),	
12.73	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 326	 [M+H]+.	 Anal.	 calcd.	 for	
C17H11NO4S:	C,	62.76;	H,	3.41;	N,	4.31.	Found:	C,	62.72;	H,	3.44;	
N,	4.38%.	

(Z)‐5‐(4‐((E)‐3‐oxo‐3‐(thiophen‐3‐yl)prop‐1‐enyl)benzylide	
ne)‐1,3‐thiazolidine‐2,4‐dione	 (5r):	 Colour:	 Yellow.	 Yield:	 82%.	
M.p.:	 204‐206	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3430	 (N−H),	 3019	
(C−H,	aromatic),	2973	(C−H,	aliphatic),	1689	(C=O),	1599	(C=C,	
aliphatic),	1414	(C=C,	aromatic),	688	(C−S).	1H	NMR	(400	MHz,	
DMSO‐d6,	δ,	ppm):	6.68	(s,	1H,	Ar‐H),	6.91	(s,	1H,	Ar‐H),	7.12	(s,	
1H,	 Ar‐H),	 7.33‐7.58	 (m,	 4H,	 Ar‐H),	 7.76	 (d,	 J	 =	 15.2	 Hz,	 1H,	
HC=CH	 (H‐α)),	 7.95	 (s,	 1H,	 HC=C),	 8.02	 (d,	 J	 =	 15.2	 Hz,	 1H,	
HC=CH	 (H‐β)),	 12.68	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 342	 [M+H]+.	
Anal.	calcd.	for	C17H11NO3S2:	C,	59.81;	H,	3.25;	N,	4.10.	Found:	C,	
59.84;	H,	3.24;	N,	4.11%.	

(Z)‐5‐(4‐((E)‐3‐oxo‐3‐(pyrrol‐2‐yl)prop‐1‐enyl)benzylidene)‐
1,3‐thiazolidine‐2,4‐dione	(5s):	Colour:	Yellow.	Yield:	85%.	M.p.:	
191‐193	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3144	 (N−H),	 3052	 (N−H),	
3017	(C−H,	aromatic),	2973	(C−H,	aliphatic),	1695	(C=O),	1615	
(C=C,	aliphatic),	1414	(C=C,	aromatic),	678	(C−S),	1308	(C−N).	
1H	NMR	(400	MHz,	DMSO‐d6,	 δ,	ppm):	6.46	(s,	1H,	Ar‐H),	7.44	
(m,	1H,	Ar‐H),	7.55‐7.61	(m,	5H,	Ar‐H),	7.76	(d,	J	=	15.2	Hz,	1H,	
HC=CH	 (H‐α)),	 7.97	 (s,	 1H,	 HC=C),	 8.03	 (d,	 J	 =	 15.2	 Hz,	 1H,	
HC=CH	 (H‐β)),	 10.55	 (s,	 1H,	 NH),	 12.64	 (s,	 1H,	 NH).	 ESI‐MS	
(m/z):	 325	 [M+H]+.	 Anal.	 calcd.	 for	 C17H12N2O3S:	 C,	 62.95;	 H,	
3.73;	N,	8.64.	Found:	C,	62.91;	H,	3.71;	N,	8.66%.	

(Z)‐5‐(4‐((E)‐3‐oxo‐3‐(pyridin‐4‐yl)prop‐1‐enyl)benzylide	
ne)‐1,3‐thiazolidine‐2,4‐dione	 (5t):	 Colour:	 Yellow.	 Yield:	 83%.	
M.p.:	 201‐203	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3127	 (N−H),	 3019	
(C−H,	aromatic),	2931	(C−H,	aliphatic),	1689	(C=O),	1604	(C=C,	
aliphatic),	 1417	 (C=C,	 aromatic),	 688	 (C−S),	 1308	 (C−N).	 1H	
NMR	 (400	 MHz,	 DMSO‐d6,	 δ,	 ppm):	 6.98	 (d,	 J	 =	 16	 Hz,	 1H,	
HC=CH	(H‐α)),	7.13‐7.69	(m,	8H,	Ar‐H),	7.78	(d,	J	=	16	Hz,	1H,	
HC=CH	 (H‐β)),	 7.97	 (s,	 1H,	 HC=C),	 12.60	 (s,	 1H,	 NH).	 ESI‐MS	
(m/z):	 337	 [M+H]+.	 Anal.	 calcd.	 for	 C18H12N2O3S:	 C,	 64.27;	 H,	
3.60;	N,	8.33.	Found:	C,	64.26;	H,	3.66;	N,	8.37%.	

(Z)‐5‐(4‐((E)‐3‐(naphthalen‐3‐yl)‐3‐oxoprop‐1‐enyl)benzyli	
dene)‐1,3‐thiazolidine‐2,4‐dione	 (5u):	 Colour:	 Yellow.	 Yield:	
87%.	 M.p.:	 211‐213	 oC.	 FT‐IR	 (KBr,	 vmax,	 cm‐1):	 3115	 (N−H),	
3019	(C−H,	aromatic),	2931	(C−H,	aliphatic),	1689	(C=O),	1604	
(C=C,	aliphatic),	1417	(C=C,	aromatic),	688	(C−S).	1H	NMR	(400	

MHz,	DMSO‐d6,	δ,	ppm):	7.62‐8.33	(m,	11H,	Ar‐H),	7.89	(d,	 J	 =	
15.2	Hz,	1H,	HC=CH	(H‐α)),	7.99	(s,	1H,	HC=C),	8.26	(d,	J	=	15.2	
Hz,	 1H,	 HC=CH	 (H‐β)),	 12.71	 (s,	 1H,	 NH).	 ESI‐MS	 (m/z):	 386	
[M+H]+.	Anal.	 calcd.	 for	C23H15NO3S:	 C,	 71.67;	H,	 3.92;	N,	3.63.	
Found:	C,	71.65;	H,	3.94;	N,	3.68%.	

	
2.3.	Enzyme	inhibition	assay	
	

The	 α‐glucosidase	 inhibitory	 potential	 of	 the	 synthesized	
compounds	(5a‐u)	was	determined	by	α‐glucosidase	inhibition	
assay	as	described	by	Pierre	et	al.	 [30].	α‐Glucosidase	activity	
was	 assessed	using	50	mM	phosphate	buffer	 at	 pH	=	7.0,	 and	
the	appropriate	PNP	(p‐nitrophenyl)	glycoside	(at	1	mM)	were	
used	 as	 substrates.	 The	 concentration	 of	 the	 enzyme	 was	
specified	 in	 each	 experiment.	 Compounds	 (5a‐u)	 at	 the	
designated	 concentration	 was	 added	 to	 the	 enzyme	 solution	
and	incubated	at	37	°C	for	30	min,	and	the	substrate	was	then	
added	to	initiate	the	enzyme	reaction.	The	enzyme	reaction	was	
carried	out	at	37	°C	for	30	min.	Product	(PNP)	was	monitored	
spectrophotometrically	by	measuring	the	absorbance	(λ	=	400	
nm).	 One	 unit	 of	 α‐glucosidase	 is	 defined	 as	 the	 amount	 of	
enzyme	liberating	1.0	μmol	of	PNP	per	minute	under	the	assay	
conditions	 specified.	 The	 enzyme	 reaction	 was	 performed	 in	
the	 above	 reaction	 conditions	 with	 inhibitors	 of	 various	
concentrations.	 Inhibition	 types	 for	 the	 compounds	 were	
determined	 by	 Lineweaver–Burk	 plots	 and	 its	 replot	 of	 slope	
versus	 the	 reciprocal	 of	 the	 substrate	 concentration.	 The	
characterization	of	secondary	structure	of	α‐glucosidase	in	the	
buffer	 solution	with	 or	without	 inhibitors	was	examined	with	
CD	spectroscopy.	The	data	obtained	from	the	experiments	were	
dealt	 with	 the	 professional	 software	 secondary	 structure	
estimation	and	Origin	6.0.	The	result	for	the	test	compound	was	
compared	with	the	positive	control	Acarbose.	The	results	of	α‐
glucosidase	inhibition	study	are	given	in	Table	1.	

	
3.	Results	and	discussion		
	
3.1.	Synthesis	
	

The	IR	spectrum	of	all	the	compounds	(5a‐u)	exhibited	the	
characteristic	 absorptions	 at	 various	 frequencies	 correspond‐
dingly	 at	 3310‐3110	 and	 1640‐1715	 cm‐1	 suggesting	 the	
presence	 of	 a	 secondary	 amine	 group	 and	 α,β‐unsaturated	
carbonyl	 group	 respectively.	 In	 the	 1H	 NMR	 spectra	 of	 5‐
benzylidene‐1,3‐thiazolidine‐2,4‐diones	(5a‐u),	a	singlet	 integ‐
rating	 for	 one	 proton	 characteristic	 of	 the	 HC=C	 group	 was	



148	 Nori	et	al.	/	European	Journal	of	Chemistry	5	(1)	(2014)	144‐149	
	
observed	in	between	δ	7.71‐8.15	ppm	and	a	singlet	integrating	
for	 one	 proton	 of	 the	 NH	 group	 was	 observed	 in	 between	 δ	
12.2‐13.4	 ppm	 as	 a	 broad	 signal	 indicating	 the	 presence	 of	
characteristic	features	of	basic	scaffold.	Further,	The	geometry	
of	 all	 5‐benzylidene‐1,3‐thiazolidine‐2,4‐diones	 (5a‐u)	 were	
assumed	 to	 be	 (Z)‐isomer	 as	 observed	 from	 the	 previously	
reported	 literature	 [31‐34].	 As	 seen	 in	 case	 of	 compound	5a,	
the	IR	spectrum	of	5a	exhibited	characteristic	−C=C−	(aliphatic)	
and	 −C=C−	 (aromatic)	 stretching	 bands	 at	 frequencies	 1645	
and	1513	cm‐1	respectively.	The	other	IR	absorptions	at	various	
frequencies	correspondingly	at	3155	and	1688	cm‐1	suggesting	
the	presence	of	a	secondary	amino	group	and	α,β‐unsaturated	
ketone	group		respectively.	The	400	MHz	1H	NMR	spectrum	of	
the	 compound	 5a	 in	 DMSO‐d6	 as	 solvent	 with	 TMS	 as	 an	
internal	 standard	 exhibited	 characteristic	 peaks	 of	 Hα	 and	 Hβ	
protons	 of	 α,β‐unsaturatedketone	 bridge	 appeared	 as	 two	
doublets,	one	doublet	at	δ	7.78	ppm	 (Hα,	 J	=	15.2	Hz)	and	 the	
other	one	at	δ	8.01	ppm	(Hβ,	J	=	15.2	Hz).	The	large	J	value	15.2	
Hz	of	both	the	protons	clearly	reveals	the	trans	geometry	at	the	
double	bond.	The	distinguishing	peaks	of	5‐benzylidene	(HC=C)	
and	NH	 protons	 appear	 as	 two	 singlets,	 one	 singlet	 at	 δ	 7.98	
ppm	 and	 the	 other	 singlet	 at	 δ	 12.74	 ppm.	 The	 ESI	 mass	
spectrum	 (positive	 ion	mode)	 of	5a	 revealed	 a	 (M+H)+	 ion	 at	
m/z	350.	Based	on	the	above	spectral	information	the	structure	
of	 the	 compound	 5a	 was	 confirmed	 as	 (Z)‐5‐(4‐((E)‐3‐(2‐
methylphenyl)‐3‐oxoprop‐1‐enyl)benzylidene)‐1,3‐thiazoli	
dine‐2,4‐dione.	
	
3.2.	α‐Glucosidase	inhibitory	activity	
	

From	 the	 analysis	 of	 in	 vitro	 α‐glucosidase	 inhibitory	
activity	 screening	 data	 (Table	 1)	 discovered	 that	 the	
compounds	5p	 and	5o	demonstrated	 comparatively	 the	most	
effective	 inhibitory	 activity,	with	 IC50	 values	 of	 6.56±0.81	 and	
8.92±0.21	µg/mL,	respectively.	It	is	remarkable	to	note	that	the	
compounds	 5b	 and	 5g	 also	 showed	 appreciable	 inhibitory	
activity	with	 IC50	values	of	15.28±0.15	and	19.20±0.37	µg/mL,	
respectively.	 The	 other	 compounds	 such	 as	5f,	5i,	5n,	5e,	5h,	
5s,	5m,	5a,	5u,	5t,	5c,	5j	and	5k	showed	reasonable	activity	at	
concentrations	 (IC50)	 ranging	 from	 23.16±0.27	 to	 39.77±0.23	
µg/mL.	The	remaining	compounds	5l,	5q,	5r	and	5d	exhibited	
less	 activity	 with	 IC50	 values	 ranging	 from	 41.82±0.14	 to	
49.17±0.14	 µg/mL	 in	 comparison	 with	 the	 standard	 drug	
(Acarbose,	 IC50	 :	 0.007±0.27	 µg/mL).	 On	 the	 basis	 of	 the	
obtained	 data	 we	 could	 develop	 interesting	 structure‐activity	
relationships	 [35‐36].	 The	 α‐glucosidase	 inhibitory	 activity	 is	
significantly	 affected	 by	 substituents	 at	 position	 1	 of	 α,β‐
unsaturatedketone	 system.	 For	 instance,	 the	 compounds	 5p	
(2,4‐di‐F‐C6H3,	 IC50:	 6.56±0.81	 µg/mL)	 >	 5o	 (2‐F‐C6H4,	 IC50:	
8.92±0.21	 µg/mL)	 >	 5n	 (2,4‐di‐Cl‐C6H3,	 IC50:	 29.47±0.32	
µg/mL)	 >	 5m	 (2‐Cl‐C6H4,	 IC50:	 32.11±0.33	 µg/mL)	 having	
halogen	substituents	either	at	ortho	or	meta	or	para	positions	
considerably	 improved	 the	 activity	 and	 the	 most	 potent	
derivative	 of	 the	 series	 was	 obtained.	 Among	 the	 diverse	
functionalities	 taken	 into	 consideration,	when	 the	 substituted	
phenyl	 ring	 was	 replaced	 with	 some	 other	 aromatic/hetero	
aromatic	 ring	 systems,	 as	 indicated	by	 its	 activity	order	 as	5s	
(Pyrrol‐2yl,	 IC50:	 30.84±0.66	 µg/mL)	 >	 5u	 (Naphthalen‐3‐yl,	
IC50:	 33.12±0.64	 µg/mL)	 >	 5t	 (Pyridin‐4‐yl,	 IC50:	 37.39±0.26	
µg/mL)	 >	 5q	 (Furan‐2yl,	 IC50:	 46.41±0.23	 µg/mL)	 >	 5r	
(Thiophen‐3‐yl,	IC50:	48.66±0.31	µg/mL)	moieties,	respectively.	
The	 activity	 was	 sustained	 when	 the	 compounds	 substituted	
with	 electron	 releasing	 groups,	 the	 activity	 order	 was	5b	 (3‐
Me‐C6H4,	 IC50:	 15.28±0.15	 µg/mL)	 >	 5i	 (2‐NH2‐C6H4,	 IC50:	
27.03±0.11	µg/mL)	>	5a	(2‐Me‐C6H4,	IC50:	33.06±0.25	µg/mL)	>	
5c	 (2‐OMe‐C6H4,	 IC50:	 38.42±0.52	 µg/mL)	 >	 5j	 (3‐NH2‐C6H4,	
IC50:	 38.42±0.52	 µg/mL)	 >	 5d	 (3‐OMe‐C6H4,	 IC50:	 49.17±0.14	
µg/mL),	respectively.	On	the	other	hand	a	trend	of	activity	was	
followed,	 when	 hydroxyl	 group	 substituted	 at	 different	
positions	 on	 the	 phenyl	 ring	 A	 of	 α,β‐unsaturatedketone	was	
found	to	be	biologically	significant	i.e.	(5g	(4,5‐diOH‐C6H3,	IC50:	

19.20±0.37	 µg/mL)	 >	 5f	 (3,5‐diOH‐C6H3,	 IC50:	 23.16±0.27	
µg/mL)	>	5e	(3‐OH‐C6H4,	IC50:	29.82±0.12	µg/mL)	>	5h	(2‐Me,	
5‐OH‐C6H3,	 IC50:	 29.82±0.12	 µg/mL),	 respectively.	 It	 is	 of	
interest	to	note	that	the	introduction	of	a	nitro	group	ortho	or	
meta	 to	 the	 phenyl	 ring	 A	 of	 α,β‐unsaturated	 ketone	
particularly	 unfavorable	 for	 the	 activity	 as	 seen	 in	 case	 of	
compounds	such	as	5k	(2‐NO2‐C6H4,	IC50:	39.77±0.23	µg/mL)	>	
5l	(3‐NO2‐C6H4,	IC50:	41.82±0.14	µg/mL).		
	
4.	Conclusion	
	

A	series	of	new	class	of	α‐glucosidase	inhibitors	is	reported,	
the	 synthesis	 of	 which	 is	 achieved	 by	 conventional	 methods.	
During	 this	 study,	 we	 have	 identified	 a	 number	 of	 5‐benzy	
lidene‐1,3‐thiazolidine‐2,4‐diones	 (5a‐u)	 exhibiting	 significant	
α‐glucosidase	 inhibitory	 properties.	 Structure	 activity	
relationship	studies	revealed	 that	substitution	at	position	1	of	
α,β‐unsaturatedketone	 is	 important	 to	 modulate	 the	 activity.	
Further	studies	determining	the	 in	vivo	antidiabetic	activity	of	
these	compounds	are	under	progress.		
	
Acknowledgements	
	

One	 of	 the	 authors	 Divakara	 Laxman	 Somayajulu	 Nori	 is	
thankful	 to	 Gitam	 University,	 Visakhapatnam,	 for	 providing	
necessary	facilities	to	carry	out	research	work.		
	
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