INTRODUCTION:

Oxadiazole are heterocyclic compounds with one oxygen and two nitrogen atoms in a five-membered ring^1,2 and they have a wide range of biological effects³. Oxadiazole is thought to be the outcome of replacing two methane (–CH=) groups with two pyridine type nitrogen atoms (–N=) in furan^2,3. For the synthesis of 1,3,4-oxadiazoles, several techniques have been documented in the literature.

Reactions of acid hydrazides (or hydrazine) with acid chlorides/carboxylic acids and direct cyclization of diacylhydrazines using a variety of dehydrating agents such as phosphorous oxychloride, thionyl chloride⁴, phosphorous pentoxide⁵, trifluic anhydride⁶, polyphosphoric acid⁷, and direct reaction of acid with (Nisocyanimino-) triphenyl chloride are developed^8-11.

Antimicrobial agents are far more vulnerable to gramme positive bacteria than antimicrobial agents are to gramme negative bacteria, according to research¹².

These differences could be explained by the fact that gram-positive bacteria have a single-layer cell wall, whereas gram-negative bacteria have a multilayered cell wall. Bacteria that are Gram negative have gram-negative bacteria do not have an exterior membrane or a distinctive periplasmic region.

The greater lipophilic structure of gram-negative bacteria's membrane, which acts as a barrier for many antimicrobial agents, contributes to their resistance to antibacterial agents. Hydrophilic chemicals are likely to be unable to enter the cell membranes of these bacteria. Gram-positive bacteria do not have an outer membrane or a sophisticated cell wall construction like Gram-negative bacteria. Antibacterial chemicals can easily destroy the gramme positive bacteria's cell wall and cytoplasmic membrane, resulting in cytoplasm leakage^13-14.

Oxadiazole is a five-membered heterocycle with the general formula C₂H₂ON₂. It has two carbons, two nitrogen, one oxygen, and two double bonds. Oxadiazole is thought to be produced from furan by substituting two pyridine type nitrogen (-N=) groups for two methane (-CH=) groups. According to the position of the nitrogen atom in the ring, there are four potential isomers of oxadiazole (1,2, 3, 4) that are numbered as indicated in Figure 1.

Figure 1: isomers of oxadiazole 1, 2, 3, 4 respectively.

The 1, 3, 4-oxadiazole isomer is the most commonly used of the four potential isomers for a variety of uses. Because of their wide spectrum of pharmacological properties, a large variety of substituted 1,3,4-oxadiazoles have gotten a lot of attention in the field of drug discovery. Because of their wide spectrum of actions, oxadiazoles have carved out a niche in the field of medicinal chemistry¹⁵.

BIOLOGICAL ACTIVITIES:

Anticonvulsant activity:

As anticonvulsant drugs, a series of novel 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles were developed and produced. The inclusion of an amino group in position 2 of the 1,3,4-oxadiazole ring and a fluoro substituent at the para position of the benzylthio moiety exhibited the best anticonvulsant action, according to convulsion testing¹⁶.

Anticonvulsant activity was investigated on hybrids of phenytoin and thiosemicarbazide, 1,3,4-oxadiazole, 1,3,4-thiadiazole, or 1,2,4-triazole. Standard maximum electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens were used in mice for preliminary anticonvulsant screening. The rotarod test was used to determine neurotoxicity. In the scPTZ test, 4 demonstrated the best protection (80 %) at a dose of 100 mg/kg¹⁷.

The anticonvulsant and neurotoxicity tests of a series of new 1,3,4-oxadiazole derivatives of phthalimide (4a-j) were carried out with satisfactory yields. In the MES screen, all of the compounds were active and less hazardous than phenytoin. Compound 4j, which has a methoxy substitution at the para position of the distal aryl ring, has emerged as the most promising anticonvulsant drug with the least amount of neurotoxicity¹⁸.

Anti- HIV agent:

Using microtiter anti-HIV assays with CEM-SS cells or fresh human peripheral blood mononuclear cells, the newly synthesized compounds were tested for their HIV inhibitory effectiveness as reverse transcriptase inhibitors. With an IC50 value of 1.44 M, compound 6b had the most activity¹⁹.

Anti- microbial agent:

Six novel 5-(1-/2-naphthyloxymethyl)-1,3,4-oxadiazole-2(3H) thione,2-amino-2-amino-2-amino-2-amino-2-amino-2-amino-2-amino-2-amino-2-amino-2-amino-2-a from 1-and/or 2-naphthol, 5-(1-/2-naphthyloxymethyl)-1,3,4-oxadiazole,5-(1-/2naphthyloxymethyl)-1,3,4-oxadiazole 2(3H)-one derivatives have been produced. At 64–256 g/ml concentrations, all of the compounds were active against S. aureus, E. coli, P. aeruginosa, Candida albicans, and Candida parapsilosis. A number of novel 2-amino 1, 3, 4oxadiazoles were synthesized, and their Schiff bases were obtained by condensation with different substituted aldehydes. The antibacterial activity of the produced compounds was tested against two Gram positive bacteria, two Gram negative bacteria, and two fungal species yeast strains^20-21.

Insecticidal- pesticidal activity:

2-(5-(Trifluoromethyl) pyridyloxylmethyl)-5-aryl-1,3,4- oxadiazole derivatives. A four-step synthetic approach was used to design and synthesized the compound. All oxadiazoles have a higher insecticidal activity, but those with fluorine on the benzene ring (II4&II5) have a substantial insecticidal activity²².

Anti-inflammatory activity:

A novel series of 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)1,3,4-oxadiazoles for selective COX2 inhibition with potent anti-inflammatory activity was developed and produced. 9g was discovered to be the most effective COX2 inhibitor, with an IC50 of 0.31 M and potential anti-inflammatory efficacy in the carrageenan-induced rat paw edema model, with an ED50 of 74.3 mg/kg. 2-[3-(4-bromophenyl) propan-3-one] is a novel series of 2-[3-(4-bromophenyl) propan-3-one] 3-(4 bromobenzoyl) propionic acid was used to make -5(substituted phenyl)-1,3,4-oxadiazoles (4a-n) with the goal of developing better anti-inflammatory and analgesic drugs with minimal or no side effects^23-24.

Anti- tuberculosis activity:

3-[5-pyridine-5-yl] 1, 3, 4-oxadiazole-2-yl] pyridines have been synthesized. Synthesized All of the produced compounds demonstrated anti-tubercular activity. However, compound 4g and 4h were discovered to have more activity than the others. The link between structure and activity, as well as mass fragmentation, have been investigated. A variety of 2-(4-nitro-pyrrol-2-yl)-5-aryl-1,3,4oxadiazole derivatives were synthesized. Compound 5e had the best antitubercular activity (0.46 g/mL), which was comparable to regular Isoniazid (0.40 g/mL)^25-26.

Cardiovascular activity:

A number of new substituted imidazole derivatives were synthesized and their hypotensive and acute cytotoxic actions were tested in vivo. Eight compounds out of seventeen showed good hypotensive and bradycardiac effects. Compounds 4c have demonstrated to be more effective than the standard medication clonidine.

The antihypertensive action of several novel (4-[3-acetyl-5-(pyridine-3-yl)-2,3-dihydro-1,3,4oxadiazole-2-yl] phenyl acetate) compounds has been discovered^27-28.

Anthelmintic activity:

Several substitutes 3-amino -1. (2,4-dinitro phenyl) -5-[(5 \ssubstituted-1,3,4-oxadiazol-2-yl)amino] -1-Hpyrazole -4-carboxyamide, as well as (5E) [4-(dimethylamino) benzylidene] -5-[4-(dimethylamino) benzylidene] -3-(5-substituted-1,3,4oxadiazol-2-yl) -2-phenyl -3,5-di hydrocarbon -4H-imidazol Different aromatic aldehydes and semi carbazide were used to synthesized -4-one with various functional groups. All of the substances were tested for anthelmintic activity²⁹.

Anti- pyretic activity:

2-[(5'-nitroindazole-1'-methyl)]-5-(pbromophenylamino)-1,3,4-oxadiazole derivatives were synthesized. The antipyretic activity of all synthesized compounds was comparable to that of acetylsalicylic acid³⁰.

Anti- Alzheimer’s activity:

3-[(5-[1-(4-Methoxyphenyl)-1H-benzimidazol-6-yl]1,3,4-oxadiazolyl sulfanyl) methyl] benzonitrile derivatives were produced. In vitro, compound 20x was found to have extremely selective and strong GSK-3 inhibitory action³¹.

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Received on 18.06.2021 Modified on 02.07.2021

Asian J. Research Chem. 2021; 14(5):389-392.

DOI: 10.52711/0974-4150.2021.00066