INTRODUCTION:

Thiazole, one of the most important Member of heterocyclic compounds possessing five-membered ring which is also found in many natural as well as synthetic agents. A large number of marine and terrestrial compounds possess thiazole ring as their basic moiety. Hence, these compounds show a wide spectrum of pharmacological activities. Vitamin B1 also possesses thiazole as basic moiety [1]. At C-2 position of thiazole can accommodate various lipophilic substitutions whereas C-4 position and the thiazole core are very prone for substitutions [2].

Aminothiazole is a heterocyclic amine consisting of a thiazole basic ring. It is also known as cyclic iso-thiourea which used as a starting material for synthesis of many drugs like Sulphur drugs, fungicides, dyes and biocides [3]. 2-Aminothiazoles show diazotization reaction when treated with nitrous acid or phosphoric acid. This reaction proceeds through protonation of the ring nitrogen attacked by NO⁺ ions and finally equilibrium reached along with this protonated form. At physiological pH, the aminothiazole rings having lesser basicity will be lesser protonated, so the net charge on the molecule will be low. In result, this can increase the ability of these molecules to cross the blood-brain barrier along with their in vivo potency [4,5].

The dyestuffs industry used this type of chemistry. Now days, it has been used as thyroid inhibitor in the treatment of hyperthyroidism and acid tartrate. Aminothiazoles, can also be used for the treatment of prion diseases, supported by studies carried out by using prion-infected neuroblastoma cell lines. For the synthesis of anti-biotics, 2-aminothiazoles are used to speed up the reactions and other substituted derivatives also used for various pharmaceutical applications [4].

Recently, due to wide utility of fluorescent molecules in organic electronics, chemo and biosensors and probes, attension is paid. The core skeletons of these molecules consist of rigid and planar fused ring aromatic units. New fluorescent molecules have been developed known as Arylaminothiazoles. These fluorescent molecules possess highly deviated structures and show fluorescence. Depending upon substituents, they show emission in range of 450 to 700nm wavelengths [5].

2-Aminothiazole derivatives, containing various functional groups at carbon and nitrogen atom in the thiazole ring possess a wide spectrum of biological activities [3]. 2-Aminothiazoles also found to have useful applications in agriculture as herbicides and fungicides. Due to structural similarities with 2-aminothiazole research on indeno [1, 2-d] thiazol-2-amines as allosteric modulators for A1 adenosine receptors have been increased in recent time [6].

Oestrogen receptors and a novel class of adenosine receptors antagonists possess aminothiazoles as a ligand. Along with aminothiazoles, derivatives of secondary cyclic amines possessing azole or aryl moiety were reported to exhibit a variety of biological activities such as anti-bacterial [7], anti-inflammatory [8], anti-fungal [9], urokinase inhibitors [10], photo-synthetic inhibition activity [11], inhibitors of cyclin-dependent kinases [19], anti-cancer [13,30,23] and inhibitors of protein phosphates [30].

2-Aminothiazoles showed great medicinal and biological interest. Many marketed drugs also possessed this heterocyclic moiety eg. Talipexole (dopamine agonist used as an antiparkinson agent), Sulfathiazole (a sulpha drug used as an anti-microbial agent), Sudoxicam (used as NSAID), Riluzole (used as anti-convulsant), Famotidine (H₂ receptor antagonist and used in the treatment of peptic ulcer and Meloxicam (used as NSAID) [31,32].

In this work, the 2-substituted aminothiazoles were synthesized in the laboratory and evaluated for their anti-microbial and cyto-toxic activity. The synthesis was carried out according Figure 1: Synthetic route of 2-substituted Aminothiazoles.

MATERIAL AND METHODS:

Chemicals and reagents:

The chemicals and reagents of analytical grade were used to synthesize all the titled compounds.

Instrumentation:

The melting points of compounds were determined by using thiele apparatus and were found to be little correct. The IR spectrum of compounds was recorded on Perkin-Elmer - RXI FTIR spectrometer by pellets of KBr. ¹H-NMR spectra were obtained by using FT-NMR (Bruker DRX-300) spectrophotometer using an internal standard-Tetramethylsilane. LC-MS (Schimadzu-2010 AT) was used to record mass spectra of compounds and Elemental Vario EL III, Carlo-Erba 1108 was used for carry out elemental analysis [37, 40, 41, 42].

Solvent System Used:

Precoated aluminium plates were used to monitor the progress of reaction Chloroform: Methanol: Pet. Ether (9: 1: 0.5), as a mobile phase. The 2-substituted aminothiazoles were synthesized according to the methods described in the literature [12, 37, 40, 43, 44].

General procedure for synthesis of compounds:

N-(4-Acetylphenyl)acetamide (25):

In a beaker, 4-Acetylaniline (1.35gm, 0.01mol) was mixed with acetic anhydride (3.78ml, 0.01mol). A steam bath was used for heating the above mixture for 1.15 hrs and cooled at room temperature for 3 hrs. Then the reaction mixture was separated through filtration and recrystallized by using C₂H₅OH to give compound (25) (1.19gm, 66.48%), m.p. 168°C.

IR (KBr) (υ, cm⁻¹): 3287 (NH), 1739 (C=O, Ar), 1681 (C=O of amide).

N-[4-(2-amino-1,3-thiazol-4-yl)phenyl]acetamide (26):

In conical flask containing N-(4-Acetylphenyl)acetamide (25) (1.79gm, 0.01mol), mixture of iodine (1.26gm, 0.01 mol) and thiourea (1.52gm, 0.02mol) was added. Then on a water bath, the above reaction mixture was heated for 11 hrs with occasional stirring. Diethyl ether was used to wash the soild mass to remove any unreacted N-(4-Acetylphenyl)acetamide. After that, sodium thiosulfate was used for washing to remove unreacted iodine. In last, water was used for washing and the product was filtered and dried. Finally, recrystallization was done from distilled water to give compound (26) (1.58 gm, 68.2%), m.p. 219°C.

IR (KBr) (υ, cm⁻¹): 3996 (NH₂ of thiazole ring), 3117 (CH₃of acetamide), 1669 cm^-1 (C=O of acetamide); ¹H NMR (DMSO-d_6, ppm): δ 2.8 (s of 3H of COCH₃), 7.13-7.39 (m, 5H of Ar-H), 7.63 (s, 1H, CH of C₅ of thiazole ring), 9.39 (s, 2H of NH₂); MS: m/z 231.7 (M⁺1); 189, 159 and 83.

N-[4-(2-{[(1E)-(Substituted-phenyl)methylene] amino}-1,3-thiazol-4yl) phenyl] acetamide(27-36):

N-[4-(2-amino-1,3-thiazol-4-yl)phenyl]acetamide (26) (2.33gm, 0.01mol) and various substituted aromatic aldehydes (0.01mol) were dissolved in 40ml of ethanol, then 2-3 drops of glacial acetic acid were added to it. Then the resulting mixture was refluxed for 5 hrs. After that, cooling was done of the reaction mixture. Filteration was done of soild mass and then it was washed from C₂H₅OH. Finally, it was recrystallized from mixture of DMF: water (1:1).

N-(4-{2-[2-(Substituted-phenyl)-4,5-diphenyl-imidazol-1-yl]-thiazol-4-yl}-phenyl)acetamide(37-46):

An equal amount of N-[4-(2-{[(1E)-(Substituted-phenyl) methylene] amino}-1,3-thiazol-4yl) phenyl] acetamide (27-36) (0.0016mol), excess of ammonium acetate (1 mol) along with benzil (0.0016mol) were dissolved in 25 ml of methanol in to a 250ml round bottom flask. Then the refluxing of resulting mixture was done for 16 hrs. Then, washing of the reaction mixture was done twicely with 35ml of H₂O to remove ammonium acetate and MgSO₄ was used for drying the content. 10ml of benzene was used for washing the resulting mass (twice) to remove traces of any unreacted benzil. Finally, the product was recrystallized with ethyl acetate to get pure compounds.

N-(4-{2-[2-(2-Chloro-phenyl)-4,5-diphenyl-imidazol-1-yl]-thiazol-4-yl}-phenyl)-acetamide (37):

m.p.189°C; Yield - 45.5%; IR (KBr) n: 3449.3 (Stretching of NH), 3021.1 (Ar, C-H stretching), 2843.7 (Stretching of CH of alkane), 1648.6 (Stretching of C=O), 1541.9 (Stretching of C=N), 1512.5 (Ar C-C stretching), 908.4 (C-S stretching of thiazole ring), 711.3 cm^-1 (Stretching of C-Cl); ¹H NMR (DMSO-d6): δ 2.46 (s, 3H of CH₃), 6.79-7.82ppm (m, 18H of H_arom; 1H of CH at C₅of thiazole ring); Calcd for C₃₂H₂₃ClN₄OS: C, 69.96; H, 3.98; Cl, 5.99; N, 11.00; S, 6.06; Found: C, 70.15; H, 4.09; Cl, 6.08; N, 10.91; S, 5.79.

N-(4-{2-[2-(4-Chloro-phenyl)-4,5-diphenyl-imidazol-1-yl]-thiazol-4-yl}-phenyl)-acetamide (38):

m.p. 194°C; Yield - 34.5%; IR (KBr) n: 3419.0 (Stretching of NH), 3058.6 (Ar C-H stretching), 2922.9 (C-H stretching of alkane), 1681.6 (Stretching of C=O), 1547.4 (Stretching of C=N), 1478.3 (C-C stretching, Ar), 957.8 (C-S stretching of thiazole ring), 761.2 cm^-1 (Stretching of C-Cl); ¹H NMR (DMSO-d₆): δ 2.59 (s of 3H of CH₃), 6.69-7.79ppm (m of 18H of H, Ar_;1H of CH at C₅of thiazole ring); MS(m/z) :(M+1) peak found, 543.03; (M+1 peak calculated, 547); Fragments : 497.02, 334, 225.19, 63.06; Calcd for C₃₂H₂₃ClN₄OS: C, 69.97; H, 4.54; Cl, 6.28; N, 10.04; S, 6.05; Found: C, 70.11; H, 4.01; Cl, 6.10; N, 9.89; S, 5.99.

N-(4-{2-[2-(3,4-Dimethoxy-phenyl)-4,5-diphenyl-imidazol-1-yl]-thiazol-4-yl}-phenyl)-acetamide (39):

m.p. 199°C; Yield - 41%; IR (KBr) n: 3388.4 (Stretching of NH), 3174.7 (Ar, C-H stretching), 2965.4 (C-H stretching of alkane), 1665.3 (Stretching of C=O), 1560.4 (Stretching of C=N), 1461.4 (C-C stretching, Ar), 1271.2 (C-O stretching of OCH₃), 934.1 cm^-1(C-S stretching of thiazole ring); ¹H NMR (DMSO-d6): δ 2.33 (s of 3H of CH₃), 3.35 (s of 6H, OCH₃), 6.94-8.11ppm (m of 17H, H,Ar_,1H, CH at C₅of thiazole ring); Calcd for C₃₄H₂₈N₄O₃S: C, 70.28; H, 5.03; N, 9.51; S, 5.20; Found: C, 71.01; H, 4.97; N, 9.61; S, 5.79.

N-(4-{2-[2-(4-Methoxy-phenyl)-4,5-diphenyl-imidazol-1-yl]-thiazol-4-yl}-phenyl)-acetamide (40):

m.p. 181°C; Yield - 49.8%; IR (KBr) n: 3480.0 (Stretching of NH), 2916.8 (Ar, C-H stretching), 2841.5 (C-H stretching of alkane), 1667.6 (Stretching of C=O), 1582.4 (Ar, C-C stretching), 1519.4 (Stretching of C=N), 1325.4 (C-O stretching of -OCH₃), 943.5 cm^-1(C-S stretching of thiazole ring); ¹H NMR (DMSO-d6): δ 2.34 (s of 3H of CH₃), 3.49 (s of 3H, OCH₃), 6.99-7.89 ppm (m of 18H, H, Ar_;1H, CH at C₅of thiazole ring); MS (m/z): M+1 peak found, 541.8 (M+1 peak calculated, 542); Fragments : 511, 482, 420, 321.79, 224, 64. Calcd for C₃₃H₂₆N₄O₂S: C, 73.04; H, 4.83; N, 10.32; S, 5.91; Found: C, 73.23; H, 4.79; N, 10.25; S, 6.01.

N-(4-{2-[2-(2-Nitro-phenyl)-4,5-diphenyl-imidazol-1-yl]-thiazol-4-yl}-phenyl)-acetamide (41):

m.p. 202°C; Yield - 45.2%; IR (KBr) n : 3444.8 (NH stretching), 2923.8 (aromatic C-H stretching), 2852.3 (C-H stretching of alkane), 1654.2 (C=O stretching), 1616.6 (C=N stretching), 1505.5 (N-O stretching, asymm.), 1460.9 (aromatic C-C stretching), 1393.1 ((N-O stretching, symm), 984.6 cm^-1(C-S stretching of thiazole ring); ¹H NMR (DMSO-d₆): δ 2.50 (s, 3H, CH₃), 6.75-7.72 ppm (m, 18H, H_arom,1H, CH at C₅of thiazole ring); Calcd for C₃₂H₂₃N₅O₃S: C, 68.93; H, 4.16; N, 12.56; S, 5.75; Found: C, 68.81; H, 4.31; N, 12.60; S, 5.69.

N-(4-{2-[2-(3-Nitro-phenyl)-4,5-diphenyl-imidazol-1-yl]-thiazol-4-yl}-phenyl)-acetamide (42):

m.p. 199°C; Yield - 52.8%; IR (KBr) n: 3467.7 (NH stretching), 3091.9 (aromatic C-H stretching), 2920.4 (C-H stretching of alkane), 1672.4 (C=O stretching), 1580.5 (aromatic C-C stretching), (1523.8 (C=N stretching), 1349.7 (N-O stretching, symm), 933.2 cm^-1(C-S stretching of thiazole ring); ¹H NMR (DMSO-d₆): δ 2.50 (s, 3H, CH₃), 6.75-7.72 ppm (m, 18H, H_arom,1H, CH at C₅of thiazole ring); MS(m/z) : M+1 peak found, 558; (M+1 peak calculated, 558); Fragments : 512.62, 220. Calcd for C₃₂H₂₃N₅O₃S: C, 68.93; H, 4.16; N, 12.56; S, 5.75; Found: C, 68.87; H, 4.25; N, 12.28; S, 5.79.

N-(4-{2-[2-(3-Hydroxy-phenyl)-4,5-diphenyl-imidazol-1-yl]-thiazol-4-yl}-phenyl)-acetamide (43):

m.p. 195°C; Yield-59.7%; IR (KBr) n: 3876.4 (phenolic OH stretching), 3420.0 (NH stretching), 3051.2 (aromatic C-H stretching), 2929.5 (C-H stretching of alkane), 1688.4 (C=O stretching), 1552.6 (C=N stretching), 1442.9 (aromatic C-C stretching), 963.2 cm^-1(C-S stretching of thiazole ring); ¹H NMR (DMSO-d₆): δ 2.10 (s, 3H, CH₃), 5.10 (s, 1H, OH), 6.75-7.72 ppm (m, 18H, H_arom,1H, CH at C₅of thiazole ring); Calcd for C₃₂H₂₄N₄O₂S: C, 72.71; H, 4.58; N, 10.60; S, 6.07; Found: C, 72.69; H, 4.65; N, 10.45; S, 6.27.

N-(4-{2-[2-(4-Hydroxy-phenyl)-4,5-diphenyl-imidazol-1-yl]-thiazol-4-yl}-phenyl)-acetamide (44):

m.p. 195°C; Yield - 46.7%, IR (KBr) n: 3414.7 (phenolic OH stretching), 3193.2 (NH stretching), 3071.0 (aromatic C-H stretching), 2921.0 (C-H stretching of alkane), 1655.8 (C=O stretching), 1560.4 (C=N stretching), 1525.0 (aromatic C-C stretching), 964.1 cm^-1(C-S stretching of thiazole ring); ¹H NMR (DMSO-d₆): δ 2.10 (s, 3H, CH₃), 5.10 (s, 1H, OH), 6.75-7.72 ppm (m, 18H, H_arom,1H,CH at C₅of thiazole ring); MS(m/z) : M+1 peak found, 528.62; (M+1 peak calculated, 528); Fragments : 312, 221, 68.06; Calcd for C₃₂H₂₄N₄O₂S: C, 72.71; H, 4.58; N, 10.60; S, 6.07; Found: C, 72.69; H, 4.65; N, 10.45; S, 6.27.

N-(4-{2-[2-(4-Dimethylamino-phenyl)-4,5-diphenyl-imidazol-1-yl]-thiazol-4-yl}-phenyl)-acetamide (45):

m.p. 211°C; Yield - 45.3%; IR (KBr) n: 3430.7 (NH stretching), 2918.1 (aromatic C-H stretching), 2850.5 (C-H stretching of alkane), 1634.6 (C=O stretching), 1553.6 (aromatic C-C stretching), 1401.0 (C=N stretching),771.3 cm^-1(C-S stretching of thiazole ring); ¹H NMR (DMSO-d6): δ 2.24 (s, 9H, CH₃), 6.61-8.13 ppm (m, 18H, H_arom,1H, CH at C₅of thiazole ring); Calcd for C₃₄H₂₉N₅OS: C, 73.49; H, 5.26; N, 12.60; S, 5.77; Found: C, 73.35; H, 5.25; N, 12.45; S, 5.71.

N-(4-{2-[2-(4-Formyl-phenyl)-4,5-diphenyl-imidazol-1-yl]-thiazol-4-yl}-phenyl)-acetamide (46):

m.p. 176°C; Yield - 44.5%; IR (KBr) n: 3562.1 (NH stretching), 3296.3 (aromatic C-H stretching), 3115.0 (C-H stretching of alkane), 1753.5 (aldehydic C=O stretching), 1658.1 (C=O stretching), 1596.0 (aromatic C-C stretching),1558.6 (C=N stretching), 963.6 cm^-1(C-S stretching of thiazole ring); ¹H NMR (DMSO-d6): δ 2.51 (s, 3H, CH₃), 6.75-7.72 ppm (m, 18H, H_arom,1H, CH at C₅of thiazole ring); Calcd for C₃₃H₂₄N₄O₂S: C, 72.92; H, 4.69; N, 10.96; S, 6.83; Found: C, 73.13; H, 4.19; N, 10.45; S, 6.44.

Figure 1: Synthetic route of 2-substituted Aminothiazoles

Biological Evaluation:

The newly synthesized novel 2-substituted-aminothiazoles were screened for their anti-bacterial activity against a panel of two gram +ve bacterial strains viz. Staphylococcus aureus and Bacillus subtilis and against a gram –ve bacterial strain viz. Escherichia coli by using cup plate method [33,45]. The anti-fungal activity of the synthesized novel 2-substituted aminothiazoles was carried out against two fungal strains viz. Candida albicans and Aspergillus niger using cup plate method [33,46]. DMF was used as control to carry out the studies against bacterial and fungal strains respectively [47,48]. The activity of the synthesized compounds was compared with standard at concentration of 100µg/ml by using Norfloxacin for anti-bacterial and Fluconazole for anti-fungal activity. Short-term cyto-toxic activity of the newly synthesized compounds was assessed by determining the percentage inhibition of Dalton's Lymphoma Ascites cells (DLA cells) and Erlichꞌs Ascites Carcinoma cells (EAC cells) by using Tryphan blue dye exclusion technique [38, 39, 40, 49].

RESULTS:

Chemistry:

The synthesis of titled compounds (37-46) was carried out as shown in scheme (figure-1). Spectral data analysis was carried out for the establishment of structure of titled compounds. The formation of compound (26) was confirmed by the existence of primary NH₂ group at 3996 cm^-1 in spectra of IR, NMR peak at δ 7.63 for thiazole proton and the (M+1) peak at m/z 231.7 followed by fragmentation peaks at m/z 190, 161 and 82. The formation of titled compounds (37 to 46) was confirmed by existence of =N-C group peaks between 1400-1616 cm^-1 in IR spectra and their NMR spectra didnꞌt show the peak of -N=CH- protons between δ 8.69-9.38. Mass spectra of newly synthesized compounds showed (M+ 1) peaks at 528.62, 542.65, 547.06 and 558.

Anti-microbial Activity:

All the synthesized 2-substituted aminothiazoles were screened for anti-bacterial activity against one gram -ve bacteria, Escherichia coli and two gram +ve bacteria Staphylococcus aureus and Bacillus subtilis (Table 1) and anti-fungal activity against two fungus, Candida albicans and Aspergilus niger (Table 2). Among, all the newly formed compounds, compounds 38 and 45 showed good anti-bacterial activity against gram -ve bacterial strain, Escherichia coli, 37 and 43 against Staphylococcus aureus, 37, 40 and 42 against Bacillus subtilis while 37, 38 and 44 showed good anti-fungal activity against Candida albicans and 39 and 44 against Aspergilus niger.

Cyto-toxic Activity:

Cyto-toxic efficacy of the synthesized compounds was assessed by determining the % inhibition of growth of Daltonꞌs Lymphoma Ascites (DLA) cells and Erlichꞌs Ascites Carcinoma (EAC) cells by employing Tryphan Blue Dye Exclusion technique (Table 3). Compounds 38 and 40 showed marked inhibitory activity against Dalton's Lymphoma Ascites cells (DLA cells) and Erlichꞌs Ascites Carcinoma (EAC) cells at 500, 250, 125 and 62.5µg/ml, concentrations.

DISCUSSION:

The synthesis of titled compounds was accomplished with 35 to 59.7 % yield in the presence of benzil as cyclizing agent along with excess of ammonium acetate. The progress of reactions was monitored by TLC using Chloroform: Methanol: Pet. Ether (9: 1: 0.5), as a mobile phase and Iodine vapours as visualizing agent. The formation of titled compounds (37 to 46) was confirmed by existence of =N-C group peaks between 1400-1616, N-H stretching peaks between 3388-3562 cm^-1 in IR spectra and their NMR spectra didnꞌt show the peak of -N=CH- protons between δ 8.69-9.38. Further, formation of compounds was confirmed by existence of NMR peaks for thiazole protons between δ 6.75-8.13. Mass spectra of newly synthesized compounds showed (M+ 1) peaks at 528.62, 542.65, 547.06 and 558. The formation of these new compounds was also confirmed by elemental analysis, by calculating the percentage of C, H, N and S.

The titled compounds having substitution at Ortho and Para positions show good anti-bacterial as well as anti-fungal activities by using Norfloxacin and Fluconazole as standard drugs, respectively (results are represented in table 1 and 2). In same manner, the compounds having substitution at para position show marked inhibitory activity againt DLA and EAC cell lines (results are represented in table 3) in terms of CTC₅₀ in range of 277.5 - ≥ 500.

CONCLUSION:

Among, all the newly synthesized compounds, compounds 38 and 45 showed good anti-bacterial activity against gram -ve bacterial strain, Escherichia coli, 37 and 43 against Staphylococcus aureus, 37, 40 and 42 against Bacillus subtilis while 37, 38 and 44 showed good anti-fungal activity against Candida albicans and 39 and 44 against Aspergilus niger.

Compounds 38 and 40 showed marked inhibitory activity against Dalton's Lymphoma Ascites cells (DLA cells) and Erlichꞌs Ascites Carcinoma (EAC cells) cells at 500, 250, 125 and 62.5µg/ml, concentrations.

Table 1: Results of Anti-bacterial efficacy of titled compounds

Name of Compounds	Diameter of Zone of Inhibition in mm (± Standard Deviation)
	*E. coli*			*S. aureus*			*B. subtilis*
	25 µg/ml	50 µg/ml	100µg/ml	25µg/ml	50µg/ml	100µg/ml	25µg/ml	50µg/ml	100µg/ml
37	7.7±0.05	9.2±0.17	10.3±0.17	8.0±0.05	10.6±0.11	12.3±0.25	10.4±0.20	12.3±0.20	15.3±0.20
38	8.6±0.11	10.7±0.05	12.3±0.17	7.8±0.11	9.6±0.03	11.1±0.12	6.5±0.15	7.1±0.05	10.6±0.12
39	3.7±0.05	7.1±0.12	11.1±0.05	4.6±0.11	8.2±0.13	10.5±0.28	6.3±0.08	7.5±0.25	11.1±0.05
40	3.1±0.05	6.4±0.23	8.6±0.11	7.4±0.24	9.2±0.12	11.2±0.11	9.4±0.24	11.5±0.18	14.5±0.14
41	5.3±0.17	6.7±0.05	9.6±0.05	3.2±0.08	6.6±0.05	7.7±0.05	5.3±0.25	6.7±0.05	10.7±0.05
42	4.7±0.08	6.5±0.12	9.4±0.18	6.3±0.16	7.3±0.17	8.6±0.14	10.4±0.20	12.5±0.15	16.7±0.17
43	3.6±0.14	5.6±0.24	8.6±0.15	7.4±0.11	11.3±0.17	13.6±0.11	7.1±0.14	9.3±0.14	11.4±0.05
44	6.7±0.17	8.6±0.09	10.6±0.05	5.6±0.18	8.6±0.05	9.7±0.12	8.4±0.20	10.6±0.05	14.5±0.25
45	10.3±0.17	12.4±0.08	14.4±0.21	8.6±0.11	10.8±0.06	11.6±0.11	7.1±0.05	9.6±0.11	12.6±0.11
46	8.5±0.25	9.3±0.17	10.3±0.17	6.6±0.11	8.6±0.14	10.6±0.14	4.4±0.20	8.4±0.08	9.6±0.11
Norfloxacin	-	-	27.3±0.13	-	-	22.3±0.10	-	-	24.5±0.69

Table 2: Results of Anti-fungal activity of synthesized compounds

Name of Compounds	Diameter of Zone of Inhibition in mm (± Standard Deviation)
	*Candida albicans*			*Aspergillus niger*
	25 µg/ml	50 µg/ml	100 µg/ml	25 µg/ml	50 µg/ml	100 µg/ml
37	7.4±0.08	8.4±0.15	10.6±0.21	5.4±0.05	6.2±0.14	7.7±0.12
38	5.3±0.05	7.3±0.25	9.5±0.05	3.6±0.21	4.5±0.03	6.1±0.16
39	2.6±0.05	3.9±0.05	6.5±0.17	6.4±0.20	7.8±0.12	10.3±0.20
40	5.6±0.14	6.3±0.20	6.2±0.12	3.2±0.05	4.3±0.18	6.2±0.15
41	2.6±0.21	4.2±0.14	6.6±0.17	3.6±0.05	6.3±0.15	5.1±0.05
42	6.5±0.14	8.5±0.14	9.4±0.20	8.3±0.14	2.7±0.08	4.2±0.17
43	3.5±0.11	4.6±0.11	7.2±0.17	4.4±0.20	6.4±0.20	7.5±0.20
44	7.2±0.15	8.5±0.20	9.8±0.05	4.6±0.24	6.5±0.11	9.6±0.24
45	4.6±0.14	5.4±0.26	7.5±0.11	5.3±0.12	7.4±0.12	8.4±0.14
46	2.1±0.08	4.3±0.23	6.6±0.08	2.3±0.05	3.3±0.17	5.6±0.12
Fluconazole			15.4±0.13			16.7±0.19

Table 3: Results of Cyto-toxic activity of synthesized compounds

DLA

EAC

Name of Compounds

Conc.

μg/ml

Live Cells Counted

No. of Dead Cells

% Growth Inhibition^a

^bCTC₅₀

μg/ml

Conc.

μg/ml

Live Cells Counted

No. of Dead Cells

% Growth Inhibition^a

^bCTC₅₀

μg/ml

500

250

125

62.5

62.85

48.57

42.85

28.57

277.5

500

250

125

62.5

31.42

45.71

51.42

65.71

277.5

500

250

125

62.5

45.71

34.28

8.5

2.8

≥500

500

250

125

62.5

51.42

77.14

88.57

91.42

≥500

500

250

125

62.5

65.71

54.28

45.71

337.5

500

250

125

62.5

37.14

40.00

57.14

62.85

337.5

500

250

125

62.5

31.42

14.28

11.42

≥500

500

250

125

62.5

74.28

71.42

88.57

85.71

≥500

500

250

125

62.5

34.28

25.71

17.14

8.5

≥500

500

250

125

62.5

54.28

68.57

80.00

94.28

≥500

^a % growth inhibition = 100 – [{(Celltotal – Celldead) ×100}/Cell_total]; ^bCTC₅₀ = conc. inhibiting 50% of percentage growth

ACKNOWLEDGEMENT:

The authors are thankful to Central Drug research Institute, Lucknow and J.S.S. college, Ooty for Spectral Analysis and Cyto-toxic activity, respectively.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

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Received on 05.05.2020 Modified on 13.07.2020

Research J. Pharm. and Tech. 2021; 14(6):3104-3110.

DOI: 10.52711/0974-360X.2021.00542