Synthesis and Biological Evaluation of Some Tetrahydroquinoline Compounds Derived from 4-Aminobenzenesulfonamid

In the present study, five compounds of 1,2,3,4-tetrahydroquinolines derivatives of 4Aminobenzenesulfonamid were prepared through Imines – Diels – Alder reaction by reacting Schiff bases with cinnamic acid and Bf3 Et2O in ethanol. The Schiff bases were synthesized by treating various aromatic aldehydes with 4-Aminobenzenesulfonamid. The structures of the synthesized compounds were determined on the basis of their FTIR, UV and C.H.N spectral data. The in vitro antibacterial and antifungal activities of the compounds were evaluated by paper disc diffusion method. The synthesized compounds were determined by using the Minimum Inhibitory Concentration (MIC).Significant antimicrobial activities were observed for some compounds of the series.


Introduction :
The chemistry of 1,2,3,4-tetrahydroquinolines is of interest among many investigations during recent years.The growing interest in them can be explained by their biological activities.Substituted tetrahydroquinolines are the core structures in many important pharmacological agents, .(1-2)many relatively simple synthetic 1,2,3,4tetrahydroquinolines are already in use or have been tested as potential drugs.(3)(4) Besides pharmaceutical applications, tetrahydroquinoline derivatives are useful as pesticides.(5) antioxidants,(6) corrosion inhibitors, (7) and active components of various dyes.(8) In addition, they also have found application in modern recording technologies.(9)(10) Consequently, synthesis methodologies for preparing tetrahydroquinoline derivatives have attracted considerable interest and several methods offering good results have been reported.(11) The nature, number, and relative location of the substituents are the key parameters to consider before choosing a method.Until now, much attention has been paid to the development of synthesis of mono functional

General
procedure for the synthesis of Schiff bases (1-5).The Schiff base was prepared by reaction of equimole of4-aminobenzenesulphonamide and substituted aromatic aldehydes.Each reactant was dissolved in a minimum amount of ethanol, then mixed together.The solution was refluxed for 8 hrs.then cool to room temperature and poured into ice cold water.The solid product was collected through filtration and then dried using drying oven at 80 ºC.The product was redissolved in ethanol for recrystalliziation and then dried to give a product.( 12) Preparation of Tetrahydro quinoline compounds ( 6-10 ) (0.019mol) of the Schiff base was Melted in a solvent toluene ( 2ml) with cinnamic acid ( 3 gm , 0.013 mol) .As the mixture was heated to complete the solubility .Then ,(3 ml) of Bf3 Et2O was added gradually to the mixture with continuous stirring by magnetic stirrer for five hrs.with room temperature 25 oC .The mixture was cooled and the solid product was filtrated and then dried and recrystalized by using the ethanol solvent .

ANTIMICROBIAL ACTIVITY
The antibacterial activity of the synthesized compounds was tested against Staphylococcus aureus, Staphylococcu epidermidis, Klebsiella pneumonia and Escherichia coli using nutrient agar medium.The antifungal activity of the compounds was tested against Candida albicans and Aspergillus niger using sabouraud dextrose agar medium .

Paper Disc Diffusion Medium
A suspension of the organisms were added to sterile nutrient agar media at 45oC and the mixture was transferred to sterile Petri dishes and allowed to solidify.Sterile discs 6mm in diameter (made from Wattmann filter paper previously sterilized in U.V. lamp) dipped in specified concentration solutions of synthesized compounds and standard were placed on the surface of agar plates.A disc dipped in DMF was also used as control.The plates were left for 1 hour at room temperature as a period of preoccupation diffusion to minimize the effects to variation in time between the applications of the different solutions.The plates were then incubated at 37 oC for 24 hours and observed for antibacterial activity.The diameters of zone of inhibition were measured and compared with that of the standard, the values were tabulated.Ciprofloxacin (50 µg g/disc) and Ketoconazole (50 µg g/disc) were used as standard for antibacterial and antifungal activity respectively.The observed zone of inhibition is presented in Table 4 MinimumInhibitory Concentration: Minimum Inhibitory Concentration (MIC) of the test compounds were determined by agar streak dilution method. 1 mg/ml stock solution of the synthesized compounds were made using DMF as the solvent.From this stock solution, required quantities of drug solutions were mixed with the known quantities of molten sterile agar media aseptically to provide the following concentrations1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 and100 g/ml.About 20 ml of the media containing the drug was dispensed into each sterile Petri dish.Then the media were allowed to get solidified.
Microorganisms were then streaked one by one on the agar plates aseptically.After streaking all the plates were incubated at 37oC for 24 hours/48 hours for bacterial and fungus activity respectively.Then the plates were observed for the growth of microorganisms.The lowest concentration of the synthesized compounds inhibiting the growth of the given bacteria/fungus was considered as minimum inhibitory concentration (MIC) of the test compounds against that bacteria or fungi on the plate.The MIC values of each compound against various bacteria and fungus were tabulated in Table 4

It is possible to clarify the mechanism of preparation of compounds tetrahydroquinolines as shown below
The newly prepared tetrahydroquinolines were characterized by spectral (UV, IR and C.H.N).The absorption bands of novel tetrahydroquinolines are totally agree with the anticipated structure.The physical characterization and spectral data are presented in Tables 1 ,2,All the synthesized compounds were evaluated for in vitro antibacterial and significant antifungal activities.Among the compounds, compounds 2 and 4 posscess significant activity against bacterial organisms whereas 3 showed very less activity.
Other compounds showed moderantibacterial activity.Compoundand 3 and 5,showed Zone of inhibition (for 50µg g/ml) and MIC of the synthesized compounds have been summarized in Table4