Synthesis of 1,3,4-Oxadiazole Derivatives with Its Antifungal Activity Evaluation

 

Anuja S. Patil*, Amit Nikam, Bhagyashree Mote, Akshay Ade, Vishal Khot,

Rushikesh Sonawane, Priyanka Bagade

Students of Rajarambapu College of Pharmacy, Kasegaon.

*Corresponding Author E-mail:

 

ABSTRACT:

Azole exhibits wide range of pharmacological properties. There is limited number of drugs are available to treat microbial infection that too have serious toxic effects the existing drugs has been suffering from the development of resistance and thus newer drugs are required with better activity profile. In this paper synthesis of 1,3,4- oxadiazole derivative with precursor salicylic acid and perform an antifungal activity.

 

KEYWORDS: 1,3,4- oxadiazole, salicylic acid, antifungal activity.

 

 

 

 

1. INTRODUCTION:

Heterocyclic compounds containing the five membered oxadiazole nucleus possess various of use. It shows various biological effects. Oxadiazole is considered to be derived from furan by replacement of methane (-CH=) group by two pyridine type nitrogen (-N=). Oxadiazoles are cyclic compounds containing one oxygen and two nitrogen atoms in a five membered ring [2-3]. In particular compounds bearing the 1,3,4-oxadizole nucleus are known to have unique anti-inflammatory, analgesic, antimicrobial, antifungal, antitumor, anticonvulsant, anthelmintic, anticonvulsant, antioxidant, herbicidal activities.[1]    

   

Salicylic acid is widely used as an anti-inflammatory agent. Salicylic acid also used as antirheumatic agent while compounds with the thiourea [-NH(CS)NH-] function shows antibacterial, antiviral, antifungal activities. The 1,3,4-oxadiazoleand 1,2,4-triazoles are known to have wide scope of biological and industrial activities.[2]

 

1,3,4-oxadiazole have an industrial application in fields of dyes, photosensitivity, electrical materials and liquid crystals. Oxadiazole have wide spectra of application. The preparation of azole derivatives useful for pharmaceutical as well as industrial use. [7,8]   

 

2. EXPERIMENTAL:

2.0: Chemistry:

The preparation of an oxadiazole derivative with the salicylic acid is given below. All the chemicals are provided through research lab Mumbai. Melting point were determined by open tube capillary method and are uncorrected. TLC was performed using silica gel G plates and visualized by UV or in iodine chamber. Column chromatography, wherever necessary was performed on a neutral silica column using appropriate eluent.

 

2.1: Synthesis of substituted ethyl carboxylate (1)

2-hydroxy salicylic acid (0.15 mole) in absolute ethanol (36 ml), con. Sulphuric acid (38 ml) was added slowly under stirring. It was refluxed on steam bath for 7-8 h, cooled and poured onto crushed ice under stirring. The pH was adjusted to 7 using 10% NaHCO3 and the mixture was then extracted with 5 x 25 ml of diethyl ether. Combined ethereal extracts were dried over anhydrous MgSO4 and solvent was removed under reduced pressure.[4]

 

2.2: Synthesis of substituted carbohydrazide (2)

The solution of (1) in absolute ethanol (40 ml) 98% hydrazine hydrate (7.5 gm) was added. Reflux it for 7-8 hr. cool it. Then diluted with sufficient ice-cold water. White colored precipitate was formed, filtered, washed with ice cold water, dried and recrystallize with ethanol. [5]

 

2.3: Synthesis of 5- substituted 1,3,4-oxadiazole-2amine (3)

The mixture (2) in 1,4 dioxane (47 ml) was added. Cyanogen bromide (1.08 gm) was then added to resulting mixture and stirred for 4 hrs. at room temperature. Diluted with water, filtered to obtain white solid then recrystallize it with ethanol.

 

2.4: Synthesis of 5- substituted-1,3,4-oxadiazole-2-substituted-aryl methamine (4a-4e)

Obtained mixture (3) added in equimolar of aldehyde (0.005 mole). Dissolve in ethanol (0.025 mole). Reflux it for 4-5 hrs. on water bath cooled to room temperature and neutralize with ice cold water. Filter it wash with cool water and recrystallize with ethanol. [3]

 

 

SCHEME: Synthesis of 1,3,4- oxadiazole derivative

 

Substituted carboxylic acid = salicylic acid

Ar-CHO =different types of aromatic aldehydes (4f-4j)

4f – O-chlorobenzaldehyde, 4g – P-dimethyl amino benzaldehyde, 4h – Cinnamic aldehyde, 4i – M-nitro benzaldehyde,

4j – P-nitro benzaldehyde.

 

3. BIOLOGICAL EVALUATION:

3.1: Antifungal activity

The antifungal activity was performed in vitro by agar well diffusion method against C. albicans and A. niger using luliconazole as standard. The culture of 48 h old grown on potato dextrose agar (PDA) were used for inoculation of fungal strain on PDA plates.an aliquot (0.02 ml) of inoculum was introduced to molten PDA and poured into a petri dish. After solidification, an appropriate, wells were made on agar plate by using cork borer (size 6.0 mm). Plates were incubated for 24-48h at 280C. the fungal activity was evaluated by measuring zones of inhibition of fungal growth. The complete antifungal analysis was carried out under strict aseptic conditions. [6]

 

 

Fig.1 zone of inhibition on agar plate.

 

Table no. 1: Antifungal activity of synthesized compounds

Sr no.

Compound no

Zone of inhibition in mm

Candida albicans

Aspergillum niger

1

4f

14.9

12

2

4g

6

6.2

3

4h

4.5

5

4

4i

7

9

5

4j

10

8.2

std

luliconazole

15

12.2

 

4. RESULT AND DISCUSSION:

The reaction scheme gives the ester (1) followed by hydrazide (2), then we get the 1,3,4- oxadiazole moiety. From that 1,3,4- oxadiazole moiety further derivatives (4a-4e) are obtained. The reaction is analyzed by the thin layer chromatography.

 

Antifungal activity of these derivative is carried out under aseptic condition. The activity performed with the well diffusion method shown in fig no 1. The zone of inhibition is measured in the mm. measuring of obtained derivatives are shown in the table no 1. Table shows that the compound 4f shows better activity than other compounds. Compound 4g,4h shows poor activity for both the fungus. Compound 4j shows the moderate activity as compare with standard.

 

5. CONCLUSION:

Newly synthesized 1,3,4-oxadiazole derivatives are synthesized by conventional method. Spectroscopic analysis confirms the structures of these compounds. Thus, the antifungal activity is done on that derivative. The antifungal study gives that some derivatives shows similar action with standard drug.

 

6. REFERENCES:

1.          Suman Bala, Sunil Kamboj, Ashok Kumar. Heterocyclic 1,3,4-oxadiazole compounds with diverse biological activities: A comprehensive review. Journal of Pharmacy Research. 2010 September 13, 3(12), 2993-2997.

2.          Zoulikha Khiati, Adil.A. Othmun, Bettche Guessas. Synthesis and Antibacterial Activity of 1,3,4-Oxadiazole and 1,2,4-Triazole Derivative of Salicylic Acid and its Synthetic Intermediates. South African Journal of Chemistry. 2007 March 5, 60, 20-24.

3.          Savithri Kumar, Basappa Chidananda, Vasantha Kumar. Crystal structure, Hirshfeld analysis and HSA interaction studies of N-[(E)-(5-bromothiophene-2-yl) methylidene]-3-hydroxynaphthalene-2-carbohydrazide. Journal of Molecular Structure. 2019 March 16, 1189,343-351.

4.          B. H. Furniss, A. J. Hannaford, P. W. G. Smith and A. R. Tatchell, Vogel’s Text Book of Practical Organic Chemistry, Addison Wesley Longman, New Delhi (1998) p.1077.

5.          F. A. Omkar, N. M. Mahfouz and M. A. Rahaman. Synthesis and Antimicrobial Activity of 2-substituted [4-(1,3,4-oxadiazol-2-ylmethyl)] phthalazine-1 (2 H)-one Derivatives. European Journal Medicinal Chemistry. 1996, 31, 819-825.

6.          O. Ates, A. Kocabalkanli, N. Cesur and G. Otuk, Synthesis and antimicrobial activity of some 5-aryl-2-[(N,N-disubstituted thiocarbamoylthio)acylamino]-1,3,4-oxadiazoles. Farmaco. 1998 August 30, 53(8-9), 541-544.

7.          C. H. Lee, H. I. Cho and K-J. Lee. Synthesis of 1,3,4-oxadiazoles having phenol or thiophenol group. Bulletin of Korean Chemcal Society. 2001,22,10,1153-1155.

8.          Y. Zhang, R-Z. Qiao, P-F Xu, Z-Y Zang, Q. Wang. Synthesis and Antibacterial Activities of 2-(1-Aryl-5-Methyl-1,2,3-triazol-4yl)-1,3,4-0xadiazole derivatives. Journal of Chinese Chemical Society, 2013 September 24 ,49(3),369-373.

 

 

 

Received on 26.04.2021            Modified on 05.05.2021           

Accepted on 10.05.2021   ©Asian Pharma Press All Right Reserved

Asian Journal of Pharmacy and Technology. 2021; 11(2):146-148.

DOI: 10.52711/2231-5713.2021.00024