Design, synthesis and in vitro microbiological evaluation of 6,6-dimethyl-7,9-diaryl-1,2,4,8-tetraazaspiro[4.5]decan-3-thiones - A new series of ‘tailor-made’ compounds

Figures & data

Scheme 1.  Some 1,2,4-triazole based antibacterial and antifungal drugs.

Scheme 2.  Synthetic route for the formation of 7,9-diaryl-6,6-dimethyl-1,2,4,8-tetraazaspiro[4,5]-decan-3-thlones.

Table I.  Physical and analytical data for 7,9-diaryl-6,6-dimethyl-1,2,4,8-tetraazaspiro[4.5]decan-3-thiones (23–27).

			Elemental analysis (%)
Compound	Yield (%)	m.p° C	C Found (calculated)	H Found (calculated)	N Found (calculated)	m/z (M^+) Molecular formula
23	55	119	68.10 (68.15)	6.82 (6.86)	15.85 (15.89)	353 C20H24N4S
24	45	110	69.39 (69.44)	7.36 (7.42)	14.68 (14.72)	381 C22H28N4S
25	50	112	64.01 (64.05)	6.80 (6.84)	13.54 (13.58)	413 C22H28N4O2S
26	60	127	61.78 (61.83)	5.66 (5.71)	14.38 (14.42)	389 C20H22F2N4S
27	50	121	56.97 (57.01)	5.21 (5.26)	13.25 (13.30)	421 C20H22Cl2N4S

Scheme 3. Proposed free radical mechanism for the conversion of thiosemicarbozones to the spiro-1,2,4-triazolidin-3-thiones.

Table II.  In vitro antibacterial activity (MIC) values for compounds 23–27.

	Minimum	Inhibitory	Concentration	(MIC)	in μg/mL
Micro organisms	Compound 23	Compound 24	Compound 25	Compound 26	Compound 27	Ciprofloxacin
S.aureus	100	12.5	6.25	100	50	25
β-H. streptococcus	200	6.25	12.5	100	200	50
V. cholerae	100	200	100	200	100	50
S. typhii	200	100	200	100	100	50
S. felxneri	100	200	100	100	50	25
E. coli	100	12.5	12.5	50	100	25
K. pneumonia	100	100	100	100	50	50
P. aeruginosa	200	6.25	6.25	50	100	25

Table III.  In vitro antifungal activity (MIC) values for compounds 23–27.

	Minimum	Inhibitory	Concentration	(MIC)	in μg/mL
Micro organisms	Compound 23	Compound 24	Compound 25	Compound 26	Compound 27	Fluconazole
A. flavus	25	50	50	12.5	6.25	50
Mucor	50	12.5	50	25	12.5	50
Rhizopus	50	25	12.5	12.5	6.25	25
M. gypsuem	100	50	50	100	100	25