Synthesis and antimicrobial activities of 1-(5-substituted-2-oxo indolin-3-ylidene)-4-(substituted pyridin-2-yl)thiosemicarbazide

A series of 1-(5-substituted-2-oxoindolin-3-ylidene)-4-(substituted-pyridin-2-yl)thio semicarbazide derivatives were synthesized by the reaction of 4-(substituted-pyridin-2-yl) thiosemicarbazide and 5-halogenated isatin derivatives. The newly synthesized compounds were characterized on the basis of spectral (FT-IR, 1 H, 13 C NMR and mass) analysis. Investigation of in vitro anti-bacterial and anti-fungal activity of synthesized compounds was done by disc diffusion method against B. subtilis, S. aureus, E. coli, P. aeruginosa, C. albicans, and A. niger . All the compounds exhibited moderate to good anti-bacterial and anti-fungal activity.


Experimental Section
General Procedures.Melting points were determined in open capillary tubes and are uncorrected. 1H and 13 C NMR spectra were recorded on JEOL GSX 400 spectrometer using TMS as an internal standard (chemical shifts in δ, ppm), IR spectra on a Shimadzu FT 8300 infrared spectrophotometer (ν max cm -1 ) and mass spectra on a JEOL MSMATE spectrometer.Microanalyses for C, H, N were performed in a Heraeus CHN Rapid Analyser.

Synthesis of 5-substituted isatin (2).
To 55 mL of concentrated sulphuric acid at 50°C was added 15 g of dry isonitrosoacetanilide derivative.The solution was heated to 80 °C and was kept at this temperature for about 10 min.Then it was cooled to rt and poured upon cracked ice.After 90 min, the 5-substituted isatin was filtered, washed several times with cold water to remove sulphuric acid and then dried in air.The yield of product was 80-82.5%.

Antibacterial activity
The compounds 3a-o were screened in vitro for their antibacterial activity against pathogenic organisms B. subtilis NCIM2063, S. aureus NCIM2079, E. coli NCIM206 and P. aeruginosa NCIM2200 using ciprofloxacin as standard and DMSO as solvent control.The disc diffusion method was performed using Muller-Hinton agar (Hi-Media) medium.After 24h of incubation at 37°C the zones of inhibition formed were measured in mm and are shown in Table 2.

Antifungal activity
The synthesized compounds were screened for their antifungal activity against Candida albicans NCIM3102 and Aspergillus niger using ketoconazole as standard.The plates were incubated at 26°C for 72 h and zones of inhibition formed were measured.The activity data are given in Table 2.

Table 1 .
Substituents used for title compounds

Table 2 .
Antimicrobial data of synthesized compounds