PURPOSEBacterial infection remains a serious threat to human lives because of their capacity to develop resistance to existing antibiotics, which is an increasing public health problem. For that reason, obtaining new types of antibacterial agents is a very important task. In this work, we reported the synthesis of new hydrazinecarbothioamides and 1,2,4-triazoles bearing 5H-dibenzo[a,d][7]annulene moiety and evaluated their antimicrobial activities.

In conclusion, in this paper we described the synthesis, spectral characterization and antimicrobial activity of six new compounds possessing the 5H-dibenzo[a,d][7]annulene moiety.

The new hydrazinecarbothioamides present two conformational isomers (axial and equatorial), which are interconvertible by middle ring inversion. Cyclization of hydrazinecarbothioamides in NaOH solution afforded the corresponding 1,2,4-triazoles-3(4H)-thiole which were separated as pure axial isomers and exist in two tautomeric forms. The preliminary results of antimicrobial activities indicated that the tested compounds exhibited a moderate or low activity against tested strains.

The new hydrazinecarbothioamides were synthesized using classical procedures, starting from 2-(5H-dibenzo[a,d][7]annulen-5-yl)acetohydrazide. Cyclization of hydrazinecarbothioamides in NaOH solution afforded the corresponding 1,2,4-triazoles-3(4H)-thiol. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and elemental analysis. Their antimicrobial activities were evaluated against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6663, Salmonella tiphimurium ATCC 14028, Shigella flexneri ATCC 12022, Candida albicans ATCC 90028.

Substituted hydrazinecarbothioamides and 1,2,4-triazoles as potential antimicrobial agents

Laura-Ileana Socea 1, Gabriel Şaramet 1, Ştefania-Felicia Barbuceanu 1, Theodora-Venera Apostol 1 , Bogdan Socea 2, Marina Panǎ 3 Manuela Anda Radu-Popescu 1

1Carol Davila University of Medicine and Pharmacy, Faculty of Pharmacy, Bucharest, Romania2Carol Davila University of Medicine and Pharmacy, Faculty of General Medicine, Bucharest, Romania3Cantacuzino NIRDMI, Bucharest, Romania

MATERIAL AND METHODS

REZULTS

CONCLUSIONS REFERENCE1. L.I. Socea, T.V. Apostol, G. Şaramet, Ş.F.

Bărbuceanu, C. Drăghici, M. Dinu, J. Serb. Chem. Soc., 2012, 77(11), 1541-1549;

2. I. Şaramet, A. Banciu, L. Socea, C. Drăghici, M.D. Banciu, Heterocyclic Communications, 2003, 9(6), 653-658.

Acknowledgments This work was supported by University of Medicine and Pharmacy “Carol Davila” Bucharest, a project number 28331/04.11.2013.

CH

C

H

CR

H

CH2-CO-NH-NH-CS-NH-R

CH2-CO-NH-NH-CS-NH-R

5

eq

5

ax

ax

2-axial 2-equatorial5

CH2-CO-NH-NH2

R-NCS

CH2-CO-NH-NH-CS-NH-R

NaOH

CH2

N

NNSH

R

CH3COOH

CH2

N

NH

NS

R

CH2-CH2R= a:p-C6H4-I, b:CH2-CH2-C6H5, c: N O

(1) (2a-c)

(3a-c)

1.2.

Comp S. aureus

P. aeruginosa

E. coli B. subtilis

S. tiphimurium

S. flexneri

C. albicans

2a >1024 1024 512 >1024 1024 512 >10242b 512 256 512 >1024 512 512 >10243a 256 512 512 128 >1024 512 >10243b 512 64 >1024 >1024 512 512 >1024

CH2-CO-NH-NH-CS-NH-R

νNH = 3141-3467cm-1

νCO =1673-1681 cm-1 νC=S =1253-1257 cm-1

IR DATA FOR NEW COMPOUNDS

N

NHN

S

R

CH2

ANTIMICROBIAL ACTIVITY OF TESTED COMPOUNDS MIC (µg/mL)

νNH = 3130-3198 cm-1

νC=N = 1561-1566cm-1

νC=S = 1213-1245 cm-1

NMR DATA FOR NEW COMPOUNDS

δ = 4.61-4.65 ppm (t)

δ = 3.53-3.75 ppm (t)δ = 9.13-10.15 ppm (s)

δ = 180.75-181.35 ppm

δ = 169.99 -170.11 ppm

N

NN

SH

R

CH2

δ = 10.97-11.58 ppm (s)

δ = 151.50-152.06 ppm δ = 166.57-168.08 ppm