Synthesis and microbiological activity of 8-hydroxy quinoline derivatives and related compounds

Transcription

1 PHARMACEUTICAL AD BIOLOGICAL EVALUATIOS February 2016; vol. 3 (Issue 1): ISS Research Article Synthesis and microbiological activity of 8-hydroxy quinoline derivatives and related compounds itin Deshmukh*, Prabhat Das, K. Karma GRY Institute of Pharmacy, Vidya Vihar, Borawan, Khargone, M.P., India *For correspondence Mr. itin Deshmukh, Asst Professor, GRY Institute of Pharmacy, Vidya Vihar, Borawan, Khargone, M.P., India. Received: 10 February 2016 Accepted: 24 February 2016 ABSTRACT Objective: Hydrazine and substituted hydrazines have tendency to take part in substitution as well as condensation reaction. The condensation with suitable carbonyl compound gives hydrazides. These hydrazides undergo cyclization under suitable condition gives 2-nitrogen atom containing heterocyclic ring system. These compounds have pronounced antibacterial activity. 1,3,4-oxadiazole constitute a unique class of nitrogen and oxygen containing five member heterocycle. During the last years considerable evidence has also accumulated to demonstrate the efficacy of 1,3,4-oxadiazole including antifungal, anticancer, anticonvulsant, insecticidal, anti-bacterial, anti-inflammatory and other biological effects. Methods: Some new Quinoline derivatives were synthesized by the reaction of Quinoline, chloroethylacetate, hydrazine hydrate and substituted benzoic acid. The structures of the various synthesized compounds were characterized on the basis of elemental analysis, IR and H 1 MR spectral data. These compounds were also screened for their antimicrobial and antifungal activity. Results: The synthesized compounds 1a and 3c showed effective antibacterial activity against Basillus substilis whereas 2b and 4d showed effective anti-fungal activity against Candida albicans and Aspergillus niger respectively. lusions: ew oxadiazole derivative compounds exhibit significant antimicrobial activity. Keywords: Quinoline derivatives, Synthesis, Oxadiazole, Anti-microbial acivity Introduction Literature surveys indicate that quinoline derivatives possess diverse pharmacological activities, including antimicrobial 1, antimalarial 2, antiviral 3, antitumor 4, immunomodulatory 5, caspase-3 inhibition 6, antileishmanial 7, local anesthetic 8, antiarrhythmic 8 and antiinflammatory activities 9. Also hydrazide constitutes one of the most versatile classes of compounds possessing a wide spectrum of activities. It has been reported that hydrazide derivatives possess antimicrobial 1,10, antimalarial 11, antiamoebic 12 and antitumor

2 Deshmukh. et al. Pharmaceutical and Biological Evaluations 2016; vol. 3 (1): activities. They have been in the focus of interest of medicinal chemists in the past decades because of the outstanding biological activities exhibited by several derivatives incorporating the heterocyclic moiety. Similarly, it is well documented that oxadiazole nucleus is associated with a variety of pharmacological actions, including bactericidal 14,15, antifungal 16, analgesic and anti-inflammatory 17 actions. In the present study some new Quinoline derivatives have been synthesized by the reaction of Quinoline, chloroethylacetate, hydrazine hydrate and substituted benzoic acid. The structure of the various synthesized compounds is assigned on the basis of elemental analysis IR and H 1 MR spectral data. These compounds were also screened for their antimicrobial and antifungal activity. KOH C 2 H 5 OH CS 2 OH OCH 2 COOC 2 H 5 H 2 H 2.H 2 O OCH 2 COHH 2 RCOOH POCL 3 Materials and Methods Synthesis of Quinoloxy ethyl acetate: A mixture of 8-hydroxy quinoline and ethyl chloro acetate and anhydrous potassium carbonate in dry acetone were refluxed on water bath for 24hrs at 70 0 c. The resultant reaction mixture was cooled and filtered. From the filtrate excess of acetone was removed by distillation. This reaction mixture of filtrate was then poured on to the ice cold water and stirred well. The organic layer was extracted with ether and further the ether layer was washed with 5% HCl and dried over anhydrous sodium sulphate. Ether layer was evaporated by drying on water bath. The resultant collected liquid was purified under reduced pressure to yield pure Quinoloxy ethyl acetate. Synthesis of quinoloxy acetic acid hydrazide: a mixture of Quinoloxy ethyl acetate, hydrazine hydrate in ethanol was refluxed for 6 hrs. from the resultant reaction mixture excess of ethanol was removed by distillation. On cooling from the resultant mixture yellow crystal of 8- hydroxy quinoline acetyl hydrazide began to separate.it was collected and recrystallized from ethanol. Synthesis of 5-[(quinoline-8-yloxy)methyl)]- 1,3,4-oxadiazole-2-thiol: A mixture of hydrazide, potassium hydroxide and carbon disulphide in ethanol was refluxed on water bath for 18 hrs. the solution was than concentrated, cooled and acidified with dilute hydrochloric acid. The solid that separate out was filtered and recrystallized with ethanol. O CH2 O SH S.o Compound R Code 1 1a -SH 2 2b -C 6H 5 3 3c -C 6H 5Cl 4 4d -C 6H 5Cl 2 5 5e -C 6H 5O 2 O CH2 O R Synthesis of 8-[(5-substituted-1,3,4-oxadiazole- 2-yl) methoxy]quinoline: A mixture of hydrazide and aromatic acid/ aryl alkanoic acid and POCl 3 were refluxed at c after cooling to room temperature the reaction mixture poured to ice cold water and kept overnight and filtered. The solid that separate out was filtered and recrystallized with ethanol. In vitro antimicrobial screening The synthesized compounds were subjected to antimicrobial screening by disc diffusion method for the determination of zone of inhibition. 136

3 Deshmukh. et al. Pharmaceutical and Biological Evaluations 2016; vol. 3 (1): Table 1: Physicochemical properties of compounds. S no. compounds Mol. formula M.W. M.P. % yield R f Solvent for recrystallisation 1 1a C 12H 9O 2 3S % 0.71 Methanol 2 2b C 18H 13O % 0.67 Ethanol 3 3c C 18H 12O 2 3Cl % 0.58 Ethanol 4 4d C 18H 11O 2 3Cl % 0.61 Ethanol 5 5e C 18H 12O % 0.86 Ether Standard drugs used for antimicrobial study: Ciprofloxacin (for anti-bacterial activity) and Ketoconazole (for anti-fungal activity). Table 2: Microorganisms used in the study. Microorganism used for antibacterial activity Microorganism used for antifungal activity Basillus aureus Candida albicans E. coli Aspergillus niger Basillus substilis Staphylococcus aureus Disc diffusion method: To the sterile nutrient agar, suspension of microorganism was added at 45 0 c and transferred to sterile petri dish and allow to solidify. Sterile discs 5 mm in diameter (made from what man filter paper sterilized in isopropyl alcohol) were dipped in solution containing samples, standard and blank were placed on surface of agar plates. The plates were standing for 1 hr at room temperature as period of pre incubation diffusion to minimize the effect of variation time between the applications of different solution. Than the plates were incubated at 37 0 c for 18 hr and observed for anti-bacterial activity. The diameter of zone of observed and presented. Results and Discussion The different derivatives of Quinoline were synthesized with good % yield. The melting point of all synthesized compound were found in open capillary tubes and readings were uncorrected. The IR spectra of compounds were done in Shimadzu FT 8300 infrared spectrophotometer by using KBr disc. The H 1 MR spectra of the synthesized compounds were recorded by ZEOL GSX 400 spectrophotometer using TMS as internal standard and DMSO as solvent. Analytical data of synthesized compounds 1a. IR spectral study (KBr) cm -1 : 33 H stretching, 2400 SH stretching, 1600 C=C,C= ring stretching, 12 C-O-C stretching symmetric, 1060 stretching symmetric H 1 MR: δ (s, 2H, OCH 2), 8.01(S, 6H, ArH,), 9.051(bs, 1H, SH) 2b. IR spectral study (KBr) cm -1 : 3 H stretching, 1700 C=C,C= ring stretching, C-O-C stretching symmetric H 1 MR: δ (S, 2H, OCH 2), 8.16(S, 6H,ArH,) 3c. IR spectral study (KBr) cm -1 : 3 H stretching, C=C,C= ring stretching, 800 C-Cl, 1240 C-O-C H 1 MR: δ 6.34 (S, 6H, ArH), 7.66 (S, 4H, 4d. IR spectral study(kbr) cm -1 : 3 H stretching, 1700 C=C,C= ring stretching, C-O-C stretching symmetric,8 C- Cl, H 1 MR: δ (S, 6H, ArH), (S, 3H, 5e. IR spectral study(kbr) cm -1 : 3 H stretching, 16 C=C,1610 C= ring stretching, C-O-C stretching symmetric, 3020 aromatic C-H str, 1360 O 2 H 1 MR: δ 5.04 (S, 6H, ArH), (S, 3H, 137

4 Deshmukh. et al. Pharmaceutical and Biological Evaluations 2016; vol. 3 (1): Table 3: Antibacterial activity of 1,3,4-oxadiazole derivatives. Compounds Anti microbial activity (Zone of Inhibition in mm) B. aureus E. coli B. substilis S. aureus 1a b c d e Ciprofloxacin (Standard) Table 4: Antifungal activity of 1,3,4-oxadiazole derivatives. Compounds Anti fungal activity (Zone of Inhibition in mm) C. albicans A. niger 1a b c d e Ketoconazole (Standard) lusions The research work was oriented towards the finding of newer oxadiazole with antimicrobial activity. The different substituted quinoline derivatives were synthesized followed by hydrozenolysis and cyclization reaction. Using different analytical techniques namely IR spectroscopy, MR spectroscopy confirm the structure of different oxadiazole. The result of this analysis showed that the expected different substituted oxadiazoles were synthesized. The newly oxadiazoles were evaluated for their antimicrobial activity. The synthesized compounds 1a and 3c showed effective antibacterial activity against Basillus substilis & 2b and 4d showed effective antifungal activity against Candida albicans and Aspergillus niger respectively. It can be concluded that the new synthesized oxadiazole derivatives exhibit significant antibacterial and antifungal activity against some tested microorganisms, may be potent antimicrobials. Funding: o funding sources Conflict of interest: one declared References 1. Abdel-Moty SG, Abdel-Rahman MH, Elsherief HA, Kafafy AH. Synthesis of some quinoline thiosemicarbazone derivatives of potential antimicrobial activity. Bull Pharm Sci. 2005;28:

5 Deshmukh. et al. Pharmaceutical and Biological Evaluations 2016; vol. 3 (1): Vlahov R, Parushev St, Vlahov J, ickel P, Snatzke G. Synthesis of some new quinoline derivatives potential antimalarial drugs, Pure Appl. Chem. 1990;62: ormand-bayle M, Bénard C, Zouhiri V, Mouscadet J, Leh H, Thomas C, et al. ew HIV-1 replication inhibitors of the styryquinoline class bearing aroyl/acyl groups at the C-7 position: synthesis and biological activity. Bioorg Med Chem Lett. 2005;15: Hazeldine ST, Polin L, Kushner J, White K, Corbett TH, Biehl J, et al. Part 3: Synthesis and biological evaluation of some analogs of the antitumor agents, 2-4-[(7-chloro-2- quinoxalinyl)oxy] phenoxypropionic acid, and 2-4- [7-bromo- 2-quinolinyl)- oxy]phenoxypropionic acid. Bioorg Med Chem. 2005;13: He J, Yun L, Yang R, Xiao Z, Cheng J, Zhou W, et al. Design, synthesis, and biological evaluation of novel 4-hydroquinoline-3-carboxamide derivatives as an immunomodulator, Bioorg Med Chem Lett. 2005;15: Kravchenko DV, Kysil VV, Ilyn AP, Tkachenko SE, Maliarchouk S, Okun IM, et al. 1,3-Dioxo- 4-methyl-2,3-dihydro -1Hpyrrolo [3,4-c]quinolines as potent caspase- 3 inhibitors. Bioorg Med Chem Lett. 2005;15: Dardari Z, Lemrani M, Bahloul A, Sebban A, Hassar M, Kitane S, et al. Antileishmanial activity of a new 8- hydroxyquinoline derivative designed 7-[5- (3 -phenylisoxazolino)methyl]-8- hydroxyquinoline: preliminary study. Farmaco. 2004;59: Goda FE, Abdel-Aziz AA, Ghoneim HA. Synthesis and biological evaluation of novel 6-nitro-5-substituted aminoquinolines as local anesthetic and anti-arrhythmic agents: molecular modeling study, Bioorg Med Chem. 2005;13: Savini L, Chiasserini L, Pellerano C, Filippelli W, Falcone G. Synthesis and pharmacological activity of 1,2,4- triazolo[4,3-a] quinolones. Farmaco. 2001;56: Omar M, Ahmed IC, Hassan AM, AboulWafa OM, Abou-Shleib H, Ismail KA. Synthesis and evaluation for antibacterial and antifungal activities of new 1-phenylhydrazono- -2-(substituted thiocarbamoyl)hydrazonopyruvaldehyde and the corres- ponding thiazoline and thiazolidinone derivatives. Alex J Pharm Sci. 1990;4: Klayman DL, Scovill JP, Bruce J, Bartosevich JF. 2-Acetylpyridine thiosemicarbazones, 8. Derivatives of 1- acetylisoquinoline as potential antimalarial agents. J Med Chem. 1984;27: Sharma S, Athar F, Maurya MR, aqvi F, Azam A. ovel bidentate complexes of Cu(II) derived from 5-nitrofuran-2- carboxaldehyde thiosemicarbazones with antiamoebic activity against E. histolytica. Eur J Med Chem. 2005;40: Hassan HY. Synthesis and chelating properties of substituted formyl pyridine thiosemicarbazones of potential biological activity. Bull Pharm Sci. 1999;22: Sengupta AK, Bajaj OP. J Indian Chem Soc. 1978;55: Mishra B, Ali R, izamuddin. Indian J Chem. 1988;27B: Adhikari AV, Badigar VV. Indian J Chem. 1988;27B: Ram VJ. Indian J Chem. 1988;27B: