1,3,4-oxadiazole-a bioactive scaffold for treating major depression-associated cognitive dysfunction

Background:Alzheimer’s disease affects millions of people worldwide,and one of its major characteristics is the accumulation of extracellular Aβpeptides in the human brain,leading to neuronal death and resulting in memory deficits,disorientation,and inappropriate behaviour.Objective and Methodology:This review study aims to develop new molecular targets for major depression-associated cognitive dysfunction and determine the mechanisms of action of 1,3,4-oxadiazole-based drug candidates.It encourages scientists to develop and synthesize drugs with low side effects to treat Alzheimer’s disease.Furthermore,the drug has shown significant improvement in memory function among dementia patients,which is due to the increased production of acetylcholine in the brain.These derivatives show a high affinity to amyloid plaques,which are thought to cause cognitive damage in patients with Alzheimer’s disease.This review study emphasizes newly developed inhibitors of amyloid deposition using the enzymeα-secretase,which cleaves amyloid precursor protein into smaller fragments that are toxic to neurons.1,3,4-Oxadiazole compounds have demonstrated no significant toxicity to the central nervous system.The antioxidant properties of 1,3,4-oxadiazoles can reduce free radicals,which play an active role in cell damage and disease.Conclusion:This review aims to provide readers with an overview of the current state of knowledge about oxadiazole-related drugs,emphasizing their biological importance.Key aspects related to the discovery and development of these drug candidates are discussed in detail,including information on their structure,biological activity,chemistry,and pharmacological properties.In addition,different derivatives discovered for Alzheimer’s disease to enhance the therapeutic efficiency of oxadiazole drugs have been comprehensively discussed in this review.

Pharmacokinetic evaluation,molecular docking and in vitro biological evaluation of 1,3,4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors

1, 3, 4-Oxadiazole derivatives(4 a–5 f) were previously synthesized to investigate their anticancer properties.However, studies relating to their antioxidant potential and signal transducer and activator of transcription(STAT) inhibition have not been performed. We investigated previously synthesized 1, 3, 4-oxadiazole derivatives(4 a–5 f) for various radical scavenging properties using several in vitro antioxidant assays and also for direct inhibition of STAT3 through molecular docking. The data obtained from various antioxidant assays such as 2, 2,-diphenyl-1-picrylhydrazyl radical(DPPH), nitric oxide, hydrogen peroxide, and superoxide anion radical revealed that among all the derivatives, compound 5 e displayed high antioxidant activities than the standard antioxidant L-ascorbic acid. Additionally, the total reduction assay and antioxidant capacity assay further confirmed the antioxidant potential of compound 5 e. Furthermore, the molecular docking studies performed for all derivatives along with the standard inhibitor STX-0119 showed that binding energy released in direct binding with the SH2 domain of STAT3 was the highest for compound 5 e(-9.91 kcal/mol).Through virtual screening, compound 5 e was found to exhibit optimum competency in inhibiting STAT3 activity. Compound 5 e decreased the activation of STAT3 as observed with Western blot. In brief, compound5 e was identified as a potent antioxidant agent and STAT3 inhibitor and effective agent for cancer treatment.

Synthesis and Fungicidal Activities of 2-Alkylthio-5-(3,4,5-tribenzyloxyphenyl)-1,3,4-oxadiazoles

Abstract： Ten novel 2-alkylthio-5-（3, 4, 5-tribenzyloxyphenyl）-1, 3, 4-oxadiazole derivatives （5a-j） were synthesized from methyl 3, 4, 5-trihydroxybenzoate by ethedfication, hydrazidation, cyclization and thioetherification reactions. The structures of 5a-j were confirmed by 1HNMR, MS spectra and elemental analysis. The results indicated that most of the compounds 5 exhibited good fungicidal activities. The activity of 5h is higher than 90% against Fusarium oxysporum and Botrytis cinereapers in 50 mg/L.

Structure and Biological Activities of Novel Triazole Compounds Containing 1,3,4-Oxadiazole Ring

Eighteen novel triazole compounds containing 1,3,4-oxadiazole groups were synthesized from 2-（1H-1,2,4-triazol-1-yl）acetohydrazide and carbon disulfide by several step reactions. The target compounds were characterized by elemental analysis, 1H NMR, 13C NMR, IR, MS, and X-ray crystallography. The results of preliminary biological tests show that all the compounds exhibit certain fungicidal activities.

Synthesis,Crystal Structure and Biological Activity of 2-(Anthracen-9-yl)-5-p-tolyl-1,3,4-oxadiazole

A novel compound,2-（anthracen-9-yl）-5-p-tolyl-1,3,4-oxadiazole（C23H16N2O）,has been synthesized by the condensation of 4-methylbenzohydrazide and anthracene-9-carbaldehyde in an ethanol solution with chloramine-T.The compound was characterized by 1H-NMR,13C-NMR,MS and single-crystal X-ray diffraction.The crystal belongs to the triclinic system,space group P with a = 7.7817（4）,b = 8.8544（5）,c = 12.4726（8） ,β = 92.8520（10）°,Z = 2,V = 826.58（8） 3,Dc = 1.352 g/cm3,Mr = 336.38,λ（MoKα） = 0.71073 ,μ = 0.084 mm-1,F（000） = 352,R = 0.0381 and wR = 0.1099.The dihedral angle between anthracene skeleton and phenyl ring is 64.19°.A total of 6354 unique reflections were collected,of which 3172 with I 〉 2σ（I） were observed.X-ray analysis indicated an offset face-to-face π-π stacking interaction between anthracene skeletons and an offset face-to-face π-π stacking interaction between phenyl ring planes.The novel compound molecules are connected through the offset face-to-face π-π stacking interactions to generate a three-dimensional network.The preliminary bioassay results showed that the novel compound exhibited significant insect growth inhibitory activity against Spodoptera litura Fabricius larvae.

Syntheses and Crystal Structures of Two New Complexes Generated from 2-（（Pyridin-3-ylmethyl）thio）-5-（6-quinolinyl）-1,3,4-oxadiazole and Ag~Ⅰ Salts

Two new Ag~Ⅰ-complexes have been synthesized based on the semi-rigid ligand 2-（（pyridin-3-ylmethyl）thio）-5-（6-quinolinyl）-1,3,4-oxadiazole（L）,obtained by the condensation reaction of 5-（6-quinolinyl）-1,3,4-oxadiazole-2-thiol and 3-chloromethyl pyridine hydrochloride. Crystallization of L with Ag OTf and Ag PF_6 in a CH_2Cl_2/MeO H mixed solvent system at room temperature affords a novel supramolecular [Ag_2L_2（CF_3SO_3）_2]（I） and a coordination polymer [Ag L（PF_6）]_n（Ⅱ）,respectively. Two complexes were characterized by TGA,X-ray powder and single-crystal diffraction.

一种新型的以三键为桥含1,3,4-Oxadiazole杂环的弯折型有机配体的合成及其结构表征

有机配体的结构及功能是合成具有新奇结构及物化性质的有机-无机配位聚合物的关键。我们通过Sonogashira-Hagihara偶合反应合成一种以三键为桥的含1,3,4-Oxadiazole杂环的纳米级的角型有机配体,并通过红外和1 HNMR表征了它们的结构。

THERMALLY STABLE POLYMERS BASED ON 1,3,4-OXADIAZOLE RINGS

In the present work, new thermally stable polymers containing 1,3,4-oxadiazole units have been synthesized through Huisgen reaction of the aromatic bis-tetrazole compounds with the aromatic/aliphatic bis-acid chlorides in pyridine as solvent. The obtained polymers are insoluble or slightly soluble in polar aprotic solvents such as DMSO and DMF. Thermal analyses of the polymers using DSC and TGA techniques showed that the polymers had improved thermal stabilities. The model reaction was also investigated and the resulting bis-1,3,4-oxadiazole compounds were characterized by conventional spectroscopic methods.

SYNTHESIS OF DERIVATIVES OF 3-β-D-XYLOPYRANOSYL-1,2,4-OXADIAZOLES

The synthesis of derivatives of 3-β-D-xylopyranosyl-1,2,4-oxadiazoles is accomplished by condensing protected β-D-xylopyranosyl amidoxime with acid anhydrides or various substituted benzoyl chlorides in good yield.The structures of now derivatives were identified by spectra and elemental analysis. The stability of 1,2,4-oxadiazole ring and mechanism of cyclization were. investigated.

Synthesis of 5,7-Dimethyl-2-(5-Substituted-1,3,4-Oxadiazole-2-yl)- Methylenethio-1,2,4-Triazolo[1,5-a]Pyrimidines as Potential Fungicides

A series of diheterocyclic compounds containing 1,2,4-triazolo [1,5-a]pyrimidine and 1, 3,4-oxadiazole were designed and synthesized starting from 2-mercapto-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine. The structure of all compounds prepared were confirmed by H-1 NMR spectroscopy and elemental analysis. The preliminary bioassay indicated that the title compounds displayed good fungicidal activity against Rhizoctonia solani.

Synthesis and Screening of New 5-Substituted-1,3,4-oxadiazole-2-thioglycosides as Potent Anticancer Agents

A series of newly 1,3,4-oxadiazole-2-thioglycoside derivatives were synthesized. The key step of this protocol is the coupling between 5-herteroaryl-1,3,4-oxadiazole-2-thione and activated sugars (cyclic or acyclic sugar analogues) in the presence of basic medium. Among of the synthesized compounds, compounds 7, 10, 11 and 13 were screened for them in vitro anticancer activity against four human cancer cells. MCF-7 (Breast), HEPG2 (Liver), HCT116 (Colon) and HEP2 (Larynx) carcinoma cell lines with IC50 values ranging from 2.08 - 8.72 μg/well. Compounds 11 and 13 were highly specific and potent for four cell lines (MCF-7, HCT116, HEPG2 and HEP2).

Photoluminescence and Electroluminescence Properties of 2,5-Bis[2,2′-bis(5-phenyl)-1,3,4-oxadiazole] Thiophene(T-OXD) and T-OXD/Poly(9-vinylcarbazole) Blends

The photoluminescence(PL) and the electroluminescence(EL) properties of a novel organic compound, 2,5-bis(2,2′-bis(5-phenyl)-1,3,4-oxadiazole(T-OXD), were studied in chloroform and in a solid thin film. The PL and the EL properties of T-OXD/poly(9-vinylcarbazole)(PVK) blends were also studied, which contained various contents of T-OXD. The PL maximum emission peaks of T-OXD/PVK blends show gradual bathochromtic-shift with the increase of the T-OXD content. The EL spectra of T-OXD/PVK devices are similar to their PL spectra, and all the EL maximum emission peaks show bathochromtic-shift compared with the corresponding PL spectra, which is ascribed to the formation of electroplex. The turn-on voltages for ITO/T-OXD:PVK/Al devices decreased from 13.5 V of the device cotaining 0.1% T-OXD(mass fraction) to 5 V of the device containing 5% T-OXD, which suggests that T-OXD improves the energy level match between T-OXD and PVK and enhances the emission efficiency. The experimental results indicate that T-OXD can be used as a good electron transporting material.

The Reductive Addition Reaction of Substituted 2-Chloromethyl-1,3,4-oxadiazole to Aldehydes and Ketones Promoted by Samarium Diiodide

1-（β-Hydroxyalkyl）-l,3,4-oxadiazole derivatives were synthesized via reductive addition reactions of 2-chloromethyl-l,3,4-oxadiazole with carbonyl compounds under mild conditions promoted by SmI2.

1,3,4-Oxadiazole as an emerging telomerase inhibitor-a promising anticancer motif

Currently,cancer is the most rapidly growing life-threatening disease after cardiovascular in the world,posing a major threat to human life.Telomerase promotes tumorigenesis and development in most cancers and dyskerin plays a crucial role in telomere maintenance.Cancer molecules are being developed continuously as a result of continuous research.A series of novel anticancer agents have been developed using telomerase inhibitors with improved specificity and pharmacokinetics.As medicinal chemistry advances,heterocyclic-based drugs find increasing applications,including anticancer agents.These properties have led to the development of five-membered aromatic rings of oxadiazoles.In order to enhance their anticancer activity,oxadiazole scaffolds can be modified.In this review,we discuss the functions and mechanism of action of the telomerase enzyme.The paper also summarizes the interaction between 1,3,4-oxadiazole inhibitors and telomerase enzymes.

One-pot synthesis,antibacterial and antifungal activities of novel 2,5-disubstituted-1,3,4-oxadiazoles

一系列新奇 2,5-disubstituted-1,3,4-oxadiazoles 从长链的 alkanoic 和 alkenoic 酸被综合了。这些混合物的结构被阐明了由元素、光谱(红外， 1H NMR， 13C NMR， MS ) 分析。而且，混合物被屏蔽为在对代表性的面板的 vitro 抗菌活性二克积极并且二个克否定的细菌。所有综合混合物也对真菌的五紧张为他们的抑制效应被测试。对测试有机体的各种各样的混合物表演有势力抑制效应。

Synthesis of 5-Substituted-3-[(2’R,4’R)-4’-Hydroxy-2’-hydroxymethyltetrahydrofuran-4’-yl]-1,2,4-oxadiazoles and Their Epimers

The syntheses of 5-substituted-3-[( 2’ R, 4’ R)-4 ’ -hydroxy-2 ’ -hydroxymethyltetra-hydrofuran-4’ -yl]D-1 ,2, 4-oxadiazoles and their epimers were accomplished with the aid of th construction of 1,2, 4-oxadiazoles by condensation of O-acylated cyanohydrins with hydroxylamine via intramolecular transacylation and subsequent cyclization.

3,4-二氢-2(1H)喹啉酮衍生物的合成研究

对3,4-二氢-2(1H)喹啉酮衍生物1,2,3(R= NO2,NH2,OH;R= H,NO2,NH2)的合成进行了研究。以苯胺和3-氯丙酰氯为原料,制得N-苯基-3-氯丙酰胺,然后经环合得到3,4-二氢-2(1H)喹啉酮,再经由硝化、还原、重氮化水解合成了一系列3,4-二氢-2(1H)喹啉酮衍生物:6-硝基-3,4-二氢-2(1H)喹啉酮(1a),6,8-二硝基-3,4-二氢-2(1H)喹啉酮(1b),6-氨基-3,4-二氢-2(1H)喹啉酮(2a),6,8-二氨基-3,4-二氢-2(1H)喹啉酮(2b),6-氨基-8-硝基-3,4-二氢-2(1H)喹啉酮(2c),6-羟基-3,4-二氢-2(1H)喹啉酮(3a)和6-羟基-8-硝基-3,4-二氢-2(1H)喹啉酮(3b),其中化合物(2c)及(3b)为新化合物。单步产率均在86%以上,路线简单,操作简便,反应条件温和。采用MS,1HNMR对产品进行了定性及结构表征。

1-取代-3-碘-1H-吡唑并[3,4-d]嘧啶-4-胺的合成

本研究报道一类1-取代-3-碘-1H-吡唑并[3,4-d]嘧啶-4-胺(1a~1e)的合成方法。以3-碘-1H-吡唑并[3,4-d]嘧啶-4-胺(2)为原料,分别与碘乙烷(3a)、碘甲烷(3b)、2-碘丙烷(3c)、碘代环丁烷(3d)及碘代环戊烷(3e)发生N-烷基化反应,得到5种1-取代-3-碘-1H-吡唑并[3,4-d]嘧啶-4-胺(1a~1e),产物结构经^(1)H NMR和ESI-MS确证。然后考察并确定该N-烷基化反应的适宜反应条件为:物料比为n(3a)∶n(2)=4∶1,N,N-二甲基甲酰胺为反应溶剂,碱为Cs_(2)CO_(3),反应温度为110℃。