Structure Mechanism Insights and the Role of Nitric Oxide Donation Guide the Development of Oxadiazole-2-Oxides as Therapeutic Agents against Schistosomiasis (original) (raw)
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1,2,4- and 1,3,4-Oxadiazoles as Scaffolds in the Development of Antiparasitic Agents
Journal of the Brazilian Chemical Society
In this review, we present the potential use of the heterocyclic oxadiazole rings in the design and synthesis of new drugs to treat parasitic infections. We intend to compare herein all the four isomeric forms of oxadiazole rings as well as discuss the differences and similarities between them. In addition, we discuss aspects on their reactivity that justify the great importance of both 1,2,4-and 1,3,4-oxadiazoles isomers when compared with their other two isomers. Although some oxadiazole isomers satisfy Hückel's rule, there are differences concerning their aromaticity, which have a great impact on the possible interactions of the oxadiazole ring with biological receptors. The set of works selected from the literature and discussed herein points out the oxadiazole core as an important and versatile scaffold in the development of new chemical entities potentially useful as antiparasitic drugs.
Identification of oxadiazoles as new drug leads for the control of schistosomiasis
Nature Medicine, 2008
Treatment for schistosomiasis, which is responsible for hundreds of thousands of deaths annually, depends almost exclusively on praziquantel. Hundreds of millions of people are treated annually with praziquantel and drug resistant parasites are likely to evolve. Phosphinic amides and oxadiazole 2oxides, identified from a quantitative high-throughput screen, were shown to be inhibitors of a parasite enzyme, thioredoxin glutathione reductase (TGR), with activities in the low micromolar to low nanomolar range. Incubation of parasites with these compounds led to rapid inhibition of TGR activity and parasite death. The activity of the oxadiazole 2-oxides was associated with a donation of nitric oxide. Treatment of schistosome-infected mice with 4-phenyl-1,2,5-oxadiazole-3carbonitrile-2-oxide led to dramatic reductions in worm burdens of 99%, 88% and 94%, from treatments against skin-, liver-, and adult-stage parasites, respectively, and egg-associated pathologies. These protective effects exceed benchmark activity criteria set by the WHO for lead compound development for schistosomiasis.
Synthesis, Evolution Anticancer and Microbial Activity of Some 1,3,4-Oxadiazoles Analogues
The Egyptian Journal of Hospital Medicine
Introduction: The need to develop anti-cancer drugs and the increasing bacteria resistance towered many antibiotics have made researchers more interested in testing the ability of synthetic derivatives to inhibit different types of microorganisms, although studying the cytotoxicity effect on various species of cancer cells. Aim: synthesis methyl nicotinate derivatives and evolution their anti-microbial and anti-cancer ability. Material and methods: a series of 1,3,4-oxadiazole heterocyclic compounds were synthesized, a nicotinoyl hydrazine was synthesized by refluxed methyl nicotinate and hydrazine hydrate. a good yield of Schiff bases was isolated by a reaction equimolar quantity of nicotinoyl hydrazine with several aromatic aldehydes. Up on Schiff bases acylation, heterocyclic compounds were collected, and synthetic derivatives were identified using Infra-Red (IR), Hydrogen Nuclear Magnetic Resonance (1 HNMR). The methyl thiazolyl tetrazolium (MTT) Method was used for the Evolution of anti-cancer activity. Well diffusion method over agar was used to determine antibacterial activity, gram-positive and gram-negative bacteria were used to test the strength of inhibition for synthesis derivatives. Results: a white solid of nicotinoyl hydrazine was isolated, different Schiff bases were separated in a high yield, and 1,3,4oxadiazole analogues were collected. The inhibition values of the prepared derivatives towards bacterial growth were measured. Cytotoxicity was an accounted for Schiff bases and 1,3,4-oxadiazole analogues. Conclusion: Three oxadiazole heterocyclic compounds show moderate activity. In contrast, two showed excellent inhibition toward cancer cell and bacteria growth greatly depending on the type and position of substituent groups in different hetero cyclic compounds.
Synthesis and biological evaluation of some 1,3,4-oxadiazole derivatives
European Journal of Medicinal Chemistry, 2010
A new series 1,3-benzoxazol-2(3H)-one hybrid compounds including coumarin, isatin 1,3,4triazole and 1,3,4-thiadiazole moieties were synthesized and biologically evaluated for their antioxidant capacities and antiurease properties. The synthesized benzoxazole-coumarin (6ae) and benzoxazole-isatin (10a-c) hybrids showed remarkable urease inhibitory activities with IC 50 (μM) ranging from 0.0306 ± 0.0030 to 0.0402 ± 0.0030, while IC 50 of standard thiourea is 0.5027 ± 0.0293. The synthesized benzoxazole-triazole (8a-c) and benzoxazole-thiadiazole (9a-c) hybrids showed similar urease inhibitory activities with IC 50 (μM) ranging 0.3861 ± 0.0379 to 0.5126 ± 0.0345. The antioxidant activity of synthesized compounds were evaluated for their antioxidant activities such as reducing power and ABTS (2,2′-azino-bis(3ethylbenzothiazoline-6-sulphonic acid) diammonium salt) radical scavenging. The results of ABTS radical scavenging activities of some of the synthesized molecules showed higher activities than standard trolox, SC 50 (μM)= 213.04 ± 18.12. One benzoxazol-coumarin (6f), two benzoxazole-isothiocyanate (7b, 7c) and two benzoxazole-triazole (8b, 8c) derivatives showed higher activities (SC 50 (μM) values, 82.
Bioscience Journal, 2022
In recent years, investigations in the field of oxadiazoles have been intensified due to their numerous therapeutic uses. Oxadiazoles are a class of compounds that exhibit several biological applications, citing antimicrobial, anti-inflammatory, anti-diabetic, anthelmintic, anti-tumor, among others. Encouraged by the biological potential of oxadiazoles, were carried out synthesis, antimicrobial evaluation and in silica studies of five (E)-3-(aryl)-5-styryl-1,2,4-oxadiazoles. In this way, (Z)-aryl-N'-hydroxybenzimidamides and ethyl (E)-cinnamate were synthesized, which were subjected to an O-acylamidoxime reaction after by dehydration using microwave irradiation to form the oxadiazole nucleus. The compounds were characterized by spectroscopic techniques, while in vitro antimicrobial activity was evaluated against S. aureus, E. faecalis, E. coli, P. aeruginosa, and against the fungus C. utilis using the microplate microdilution method. Thus, (Z)-aryl-N'-hydroxybenzimidamides, ...
3,4-Oxadiazole: A New Profile of Biological Activities
2014
The small and simple 1,3,4-oxadiazole nucleus is present in compounds involved in research aimed at evaluating new products that possess interesting biological activities, such as antimicrobial, antitumor, anticonvulsant, antiviral, analgesic and antiinflammatory. The present review focuses on the 1,3,4-oxadiazole with potential activities that are now in development. INTRODUCTION: 1,3,4-Oxadiazoles are unicyclic ring system which found to have diverse chemical reactivity and broad spectrum of biological activity. Although they have been known from long ago to be biologically active, their varied biological features are still of great scientific interest. 1,3,4-oxadiazole show antitumor activity, especially the phenyl-substituted 1,3,4-oxadiazole 1-2 , while phenacyl-1,3,4-oxadiazole exert ulcerogenic activity 3. Recently, Zheng Li et al. 4 have described the synthesis of 2-(3-methylbenzoylamino)-5-aryloxymethyl-1,3,4oxadiazoles as potential monoamine oxidase inhibitor. Given below is a brief account of various alterations conducted on 1,3,4-oxadiazole ring and their associated biological activities. ANTIMICROBIAL ACTIVITY: 1,3,4-oxadiazole show a wide spectrum of antimicrobial activity and a considerable amount of work has been done on the synthesis of new potent antibacterial and antifungal 1,3,4-oxadiazoles. Khanum, S.A. et al 5 , prepared some new 5-(2-aroylaryloxy)methyl-1,3,4-oxadiazole-2-(3H)thiones (1) and screened them for their antibacterial activity against E.coli, B.subtilis, P.fluorescens, P.solanacearum, and for their antifungal activity against C.albicans, C.krusei, C.parapsilosis, A.flavus, A.ochraceous, F.moniliforme. The antifungal screening results have been shown that the halo substituted compounds exhibit significant activity. In case of antibacterial activity all the compounds have shown higher activity.
Chemistry Africa
The synthesis of 2-(5-methyl-2-nitrophenyl)-5-(substituted)-1,3,4-oxadiazoles (5a-e) and thiadiazoles (6a-e) was carried out by refluxing of N-(5-methyl-2-nitrobenzoyl)-2-substituted carbohydrazide with phosphorous oxychloride and Lawesson's reagent respectively. The N-(5-methyl-2-nitrobenzoyl)-2-substituted carbohydrazides was synthesized by treating 2(5-methyl-2-nitrobenzohydrazide) with various aryl acids in the presence of HATU and DIPEA. Compounds 6a, 5c and 5d exhibited significant cytotoxic properties when compared to standard podophyllotoxin. Further, the compounds were also studied for their antibacterial activities.
A review on synthetic account of 1,2,4-oxadiazoles as anti-infective agents
Molecular Diversity, 2022
Most of the currently marketed drugs consist of heterocyclic scaffolds containing nitrogen and or oxygen as heteroatoms in their structures. Several research groups have synthesized diversely substituted 1,2,4-oxadiazoles as anti-infective agents having anti-bacterial, anti-viral, anti-leishmanial, etc. activities. For the first time, the present review article will provide the coverage of synthetic account of 1,2,4-oxadiazoles as anti-infective agents along with their potential for SAR, activity potential, promising target for mode of action. The efforts have been made to provide the chemical intuitions to the reader to design new chemical entity with potential of anti-infective activity. This review will mark the impact as the valuable, comprehensive and pioneered work along with the library of synthetic strategies for the organic and medicinal chemists for further refinement of 1,2,4-oxadiazole as anti-infective agents.
Synthesis, antimicrobial activity and cytotoxicity of novel oxadiazole derivatives
Journal of Enzyme Inhibition and Medicinal Chemistry, 2012
In the present study, 5-substituted-1,3,4-oxadiazolin-2-thiones (1a-b) were synthesized via the ring closure reactions of appropriate acid hydrazides with carbon disulphide. N-(Benzothiazol-2-yl)-2-[[5-substituted-1,3,4-oxadiazol-2-yl] sulfanyl]acetamide derivatives (3a-j) were obtained by the nucleophilic substitution reactions of 5-substituted-1,3,4-oxadiazolin-2-thiones (1a-b) with N-(benzothiazol-2-yl)-2-chloroacetamides. The chemical structures of the compounds were elucidated by IR, 1 H NMR, 13 C NMR and FAB +-MS spectral data and elemental analyses. The synthesized compounds were screened for their antimicrobial activities against Micrococcus luteus, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Listeria monocytogenes and Candida albicans. All compounds except compound 3h exhibited the highest antibacterial activity against P. aeruginosa. Among all compounds (3a-j), the compounds bearing 4-methoxyphenoxymethyl moiety on oxadiazole ring (3a-e) exhibited the highest inhibitory activity against C. albicans. Although compound 3j did not possess 4-methoxyphenoxymethyl moiety on oxadiazole ring, this derivative also exhibited the same level of anti-candidal activity. The compounds were also investigated for their cytotoxic effects using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Compound 3a exhibited the highest cytotoxic activity, whereas compound 3g possessed the lowest cytotoxic activity against NIH/3T3 cells.