Synthesis and Antibacterial Assessment of N-[4-(4-substituted phenyl)-1,3-thiazol-2-yl]-1,3,5-triazin-2-amine

In a wide search program towards new and efficient antibacterial agents, we assessed the extent to which physicochemical properties can be exploited to promote antibacterial activity associated with a series of substituted s-triazine. The synthesized compounds (1a-12b) were subsequently screened for their in vitro antibacterial activity against three gram positive (Bacillus subtilis, Bacillus cereus, Staphylococcus aureus) and three Gram-negative microorganism (Salmonella typhi, Escherichia coli, Klebsiella aerogenes) by the broth dilution technique, recommended by European Committee for antimicrobial susceptibility testing with reference to streptomycin.

and the ointment was then applied to the hole and time for diffusion was noted evidenced by pink rings on agar medium after particular interval [9][10][11] .
Rice bran wax base appeared shining yellowish white with less wash ability as that of shining white colored standard base.The results show that rice bran wax base has good spreadability (average spreadability 16.8±2.4)as that of standard base (average spreadability 10.13±1.66).Ointment prepared with rice bran wax base showed good diffusibility (average diffusibility 0.6±0.057)than the ointment which was prepared using standard base (average diffusibility 0.4±0.057)and also showed decrease in water number as compared to standard base which represents its less water absorbing capacity (1.5 ml vs 2.0 ml for standard base).Thus results show that, rice bran wax acts as an oleaginous ointment base as far as its pharmaceutical properties are concerned against the available costly bases.
The extraordinary progress represented by the arrival of antibiotics has changed the medical prognosis of minor and major infections.However, over the years via several constantly changing mechanisms, many bacterial species acquired resistance to the most common classes of antibiotics.A relevant report on resistant antibacterial agents for human medicine is provided by World Health Organization.The panel agreed that the list of critically important antibacterial agents should be updated regularly as new information becomes available, including data on resistance patterns, new and emerging diseases and the development of new drugs [1] .
During the last few years the potential of s-triazine derivatives in molecular recognition, agrochemical and medicinal properties have been subjected to investigation.Literature survey reveals that substituted s-triazine derivatives are associated with number of pronounced antibacterial activities [2][3][4] against gram positive (B.subtilis, B. cereus and S. aureus) and gram negative organism (S. typhi, E. coli and K. aerogenes).The biological activity is a function of physicochemical properties of the targeted molecule and this assessment is made of the sorts of chemicals that might fit into an active site [5,6] .To randomly explore the novel compounds, our idea was to combine, cyanuric chloride with various amines possessing distinguish physicochemical properties.The substituted phenylthiazole-2-amine derivatives remain attractive, with their significant biological activities [7,8] and further incorporation of these derivatives giving access to a wide array of structures, which can be expected to show interesting antibacterial activities.In this wide search program, here we demonstrate various amines mediated substitution in cyanuric chloride and subsequently with higher bioactive, 4-sustituted phenylthiazole-2-amine to synthesize N-[4-(4-substituted phenyl)-1,3-thiazol-2-yl]-1,3,5triazin-2-amine derivatives (scheme 1).
The MIC values (Table 1) of this class of synthesized compounds against tested organism displayed a significant activity with wide degree of variation (4-128 µg/ml).The preliminary antibacterial results showed that diamino-s-triazine (1a-3a) derivatives were significantly less active, among them diphenylamine substituted s-triazine were more efficient substituent for the entire tested microorganisms.Further a considerable difference in antibacterial activity between (1a-3a) disubstituted, diamino-s-triazine (MIC= 16-128 µg/ml) and (4b-12b) trisubstituted, N-[4-(4-substitutedphenyl)-1,3-thiazol-2-yl]-1,3,5-triazin-2-amine (MIC= 4-64 µg/ml), emphasized the importance of incorporating bulky groups.All of the biologically active substituted s-triazine derivatives show lipophilic traits.Possibly, this is because of the enhanced ability of compound to penetrate the cell permeability barrier.The  Today up to 75% of antibiotic use is said to be of questionable therapeutic value, antibiotic use is the against three gram positive (Bacillus subtilis, Bacillus cereus, Staphylococcus aureus) and three Gram-negative microorganism (Salmonella typhi, Escherichia coli, Klebsiella aerogenes) by the broth dilution technique, recommended by European Committee for antimicrobial susceptibility testing with reference to streptomycin.

TABLE 1 : In VItro ANTIBACTERIAL ACTIVITY OF THE SYNTHESIZED COMPOUNDS
*DMSO as negative control