Synthesis and evaluation of newly1-substituted-(2H)-2-thio-4-(3-substitutedthiocarbamido-1-yl)-6-(2-imino-4-thio-5- substitutedbiureto-1-yl) 1, 2-dihydro-S-triazines as potent antimicrobial agents

The search for novel antibiotics is of immense importance in research areas around the world for agricultural, pharmaceutical, and industrial applications. The s-triazines are widely used as an important biological tool for the production of a wide range of novel secondary metabolites. In the present study, the series of 1-substituted-(2H)-2-thio4-(3substitutedthiocarbamido-1-yl)-6-(2-imino-4-thio5substitutedbiureto-1-yl) 1,2-dihydro-s-triazine [4a(i) to 4f(iii)] have been obtained by the isomerisation of 2-(2-imino-4-thio-5substitutedbiureto-1-yl)-4-(3substitutedthiocarbamido-1-yl)-6substitutedimino-1,3,5-thiadiazine [3a(i) to 3f(iii)] in presence of ethanolic sodium bicarbonate solution. The later were synthesized by the chemical action of 1, 3-bis-(N-phenylamidinothiocarbamido)-thiocarbamide and aryl/alkylisocyanodichlorides. On the basis of IR, PMR spectrum data and elemental analysis, the structures of all these compounds were established. The synthesized s-triazine were analyzed for antimicrobial activities by cup plate diffusion method and exhibited a broad spectrum of antimicrobial activity against test pathogens. The isolate was tested for the ability to grow in the presence of antibiotic, such as ciprofloxacin at the same concentration. Thus, the study concludes with the eco-friendly route for synthesizing s-triazine with antibacterial activity against clinically important pathogens.


Introduction
The heterocyclic compounds containing triazine nucleus gain enormous significance in human life due to their applications in pharmaceutical, industrial, medicinal, agricultural values. s-triazines possess potential therapeutic value for several diseases. Some s-triazines act as antibacterial [1][2][3], anti-inflammatory, antidiabetic , hypoglycemic agent , and muscle relaxant. They are also used as herbicidal, sea water algicidal, insecticidal [4], and bacteriocidal [5][6][7], some of them have been used as chain lengthening agents in polymerization, paints, plastic and rubber. In the view of the utility of those compounds in various fields. It was thought interesting to investigate the biological activities of synthesized s-triazines.

Experimental Section
All chemical used were of analar grade, 1,3-bis (N-phenylamidinothiocarbamido) thiocarbamide [8] and Naryl/alkylisocyanodichlorides were prepared according to literature method [9]. Melting point of all synthesized compounds was determined by open capillary method. IR spectra were recorded on Perkin-Elmer spectrometer in the range 4000-400 cm -1 in Nujol mull as KBr pelletes. PMR spectra were recorded with TMS as internal standard using CDCl3 and DMSO-d6. TLC checked the purity of the compounds on silica gel-G plates with layer thickness of 0.3mm. All compounds gave satisfactory C, H, N and S elemental analysis. All Synthesized s-triazine were screened for their antimicrobial activity using cup plate diffusion method [10][11]. Both gram-positive and gram-negative bacterial organisms viz. S. aureus, B. subtilis, A. aerogenes, E. coli, and S. typhi were used for microbial activities.
Similarly others compounds [3a(i) to 3f(iii)] were synthesized by above stated scheme.

Properties of Compound [4a (iii)]
It is crystalline pale yellow solid having m.p. 243 0 c. From analytical data, the molecular formula of compound [4a(iii)] is C20H21N9S3. IR spectra of compound shows 3435. Similarly other compounds were synthesized from [3a (i)] to [3f (iii)]) and which on isomerizes yielded [4a (i)] to [4f (iv)] by above method and enlisted in table 1.

Results and discussion
All the synthesized compounds were effectively characterized by their IR, UV and PMR spectral analysis and elemental analyses. They were also assayed for their antimicrobial activity against both gram-positive and gram-negative human pathogens and found that they possess insecticidal, bactericidal and medicinal values.

Conclusion
As newly s-triazines shows remarkable antimicrobial activity, these compounds can be easily used as alternative drugs for the treatment of various diseases.