Synthesis and Study of Some Newer Analogues of Quinolin-8-ol as Potent Antimicrobial Agents

New series of 4-(substituted phenyl)-5-[(quinolin-8-yloxy) methyl]4H-1,2,4-triazole-3-thiol (4a-c), N3-(4-substituted phenyl)-5-[(quinolin-8-yloxy) methyl]-4H-1,2,4-triazole-3,4-diamine (5a-c) and N-(4-substituted phenyl)-5[(quinolin-8-yloxy) methyl]-1,3,4-thiadiazol-2-amine (6a-g) have been synthesized and the structures of the new compounds were established on the basis of IR, H NMR spectral data. In vitro antimicrobial activity (MIC activity) was evaluated and compared with standard drugs of loxacin and ketoconazole. Compounds 5a and 6e in the series have shown interesting antibacterial activity against both S. aureus (gram-positive) and E. coli (gram-negative) organisms. In this paper, we also describe studies leading to identification of antifungal agents. In the gratifying result, most of the compounds were found to have moderate antimicrobial activity.


Introduction
Heterocycles bearing a symmetrical triazole or 1,3,4-thiadiazole moieties represent an interesting class of compounds possessing a wide spectrum of biological activities such as anti-inflammatory [1][2][3] , antiviral 4 and antimicrobial 5,6 properties.It has also been reported in literature that derivative of 1,2,4-triazole and 1,3,4-thiadiazole condensed nucleus systems found that have diverse pharmacological activities such as antiinflammatory 7 antitumor 8 , antifungal and antibacterial 9 .Furthermore, literature survey revealed that modification of the carboxyl function of representative non-steroidal anti-inflammatory drugs (NSAIDs) resulted in an increased anti-inflammatory activity with reduced ulcerogenic effect [10][11][12] .Our former studies 13,14 have shown that certain compounds bearing 1,2,4-triazole and 1,3,4-thiadiazole nuclei possess significant anti-inflammatory activity with reduced gastrointestinal (GI) toxicity.we describe herein the synthesis of some triazole, thiadiazole derivatives and evaluation of their antimicrobial activities.The reaction sequence leading to the formation of desired heterocyclic compounds are outlined in Scheme 1.The structures of the compounds were assigned on the basis of IR, 1 H NMR spectral data. (1)

Experimental
Melting points were determined in open capillary tubes.IR spectra were recorded on a perkin-Elmer 157 spectrometer and 1 HNMR spectra on a Bucker WM-400 (400 MHZ FT NMR) spectrophotometer using TMS (Tetramethyl Silane) as internal reference (chemical shift in δ ppm).Purity of the compounds was checked by TLC (Thin Layer Chromatography) on silica gel plates and spot were visualized by exposure to iodine vapours.The physical data of the compounds prepared are presented in Table 1.

2-(Quinolin-8-yloxy) acetohydrazide (2)
To a RB flask, compound 1 (0.01 mol), hydrazine hydrate (0.2 mol) and absolute alcohol (50 mL) were taken.A condenser with calcium guard tube was attached to the flask and mixture was refluxed for 24 hours on water bath.The mixture was concentrated, cooled and poured in crushed ice.It was kept for 3-4 hours at room temperature and solid mass separated out was filtered and dried, recrystallised in methanol. 1

Spectral characterization of the compounds
The IR spectrum of the compounds (4a-c) showed peaks at 3361-3370 cm -1 , N─H stretching; 2922-2935 cm -1 , CH stretching; 1577-1601 cm -1 , C=N stretching and 1186-1216 cm -1 , C=S stretching.The NMR spectrum of the compound 4a showed a singlet at δ 3.89 indicating the presence of OCH 2 protons.In the aromatic region complex multiplete at δ 7.25-7.88was observed indicating the presence of ten aromatic protons.A singlet at δ 10.52 was observed for one SH protons.The NMR spectrum of the compound 4c showed a singlet at δ 3.84 indicating the presence of OCH 2 protons.In the aromatic region complex multiplete at δ 7.28-7.78was observed indicating the presence of ten aromatic protons.Furthermore a singlet at δ 10.60 was observed for one SH protons.The IR spectrum of the compounds (5a-c) showed peaks at 3245-3296 cm -1 , N─H stretching; 2928-2938 cm -1 , CH stretching; 1618-1624 cm -1 , C=N stretching.The NMR spectrum of the compound 5a showed a singlet at δ 2.28 indicating the presence of CH 3 protons.In the aromatic region complex multiplete at δ 7.05-7.98was observed indicating the presence of ten aromatic protons.A broad singlet at δ 8.24 was observed for one NH protons.
The NMR spectrum of the compound 5b showed a singlet at δ 2.48 indicating the presence of OCH 3 protons.In the aromatic region complex multiplete at δ 7.08-7.96was observed indicating the presence of ten aromatic protones.A broad singlet at δ 8.26 was observed for one NH protons.The IR spectrum of the compounds (6a-g) showed peaks at 3418-3436 cm -1 , N─H stretching; 2928-3039 cm -1 , CH stretching; 1610-1660 cm -1 , C=N stretching.The NMR spectrum of the compound 6a showed a singlet at δ 5.44 indicating the presence of OCH 2 protons.In the aromatic region complex multiplete at δ 7.23-7.67was observed indicating the presence of ten aromatic protons.A singlet at δ 7.98 was observed for one NH protons.The NMR spectrum of the compound 6f showed a singlet at δ 5.46 indicating the presence of OCH 2 protons.In the aromatic region complex multiplete at δ 7.28-7.97was observed indicating the presence of ten aromatic protons.Furthermore a singlet at δ 7.96 was observed for one NH protons.

Conclusion
In summary, we have described the genesis and synthesis of antimicrobially The antimicrobial screening results revealed that some of the compounds are moderately active.However, the activities of the tested compounds are less than those of standard antibacterial and antifungal agents used.

Table 1 .
Characterization data of the compounds.

Table 2 .
Antimicrobial activities of the compounds.