3004-42-0Relevant articles and documents
Synthesis of new 1, 3, 4-oxadiazole-incorporated 1, 2, 3-triazole moieties as potential anticancer agents targeting thymidylate synthase and their docking studies
Alam, Mohammad Mahboob,Almalki, Abdulraheem S. A.,Neamatallah, Thikryat,Ali, Nada M.,Malebari, Azizah M.,Nazreen, Syed
, p. 1 - 15 (2020)
Thymidylate synthase (TS) has emerged as a hot spot in cancer treatment, as it is directly involved in DNA synthesis. In the present article, nine hybrids containing 1,2,3-triazole and 1,3,4-oxadiazole moieties (6–14) were synthesized and evaluated for anticancer and in vitro thymidylate synthase activities. According to in silico pharmacokinetic studies, the synthesized hybrids exhibited good drug likeness properties and bioavailability. The cytotoxicity results indicated that compounds 12 and 13 exhibited remarkable inhibition on the tested Michigan Cancer Foundation (MCF-7) and Human colorectal Carcinoma (HCT-116) cell lines. Compound 12 showed four-fold inhibition to a standard drug, 5-fluoruracil, and comparable inhibition to tamoxifen, whereas compound 13 exerted five-fold activity of tamoxifen and 24-fold activity of 5-fluorouracil for MCF-7 cells. Compounds 12 and 13 inhibited thymidylate synthase enzyme, with an half maximal inhibitory concentration, IC50 of 2.52 μM and 4.38 μM, while a standard drug, pemetrexed, showed IC50 = 6.75 μM. The molecular docking data of compounds 12 and 13 were found to be in support of biological activities data. In conclusion, hybrids (12 and 13) may inhibit thymidylate synthase enzyme, which could play a significant role as a chemotherapeutic agent.
Nickel(II) complexes of 5-phenyl and 5-furan-1,3,4-oxadiazole-2-thiones containing ethylenediamine: Synthesis, spectral and X-ray characterization
Singh, Nand K.,Bharty, Manoj K.,Kushawaha, Surendra K.,Butcher, Raymond J.
, p. 205 - 211 (2010)
The products obtained by the reactions of Ni(OAc)24H 2O with Hpot (Hpot = 5-phenyl-1,3,4-oxadi-azole-2-thione) and [K(H2fchc)] (potassium N'-(furan-2-carbonyl) hydrazine carbodithioate), on treatment with excess of ethylenediamine (en), gave mixed ligand complexes [Ni(pot)2(en)2](1) and [Ni(fot) 2(en)2](2) (fot = 5-furan-(1,3,4)-oxadiazole-2-thione). These complexes have been characterized with the aid of elemental analyses, IR, magnetic susceptibility and single crystal X-ray studies. In both complexes, the heterocyclic ligand coordinates through oxadiazole nitrogen, and the ligand exists as the thione form. The complexes 1 and 2 have distorted octahedral geometries around the centrosymmetric Ni(II) center with trans oxadi-azole ligands. Both complexes show extended hydrogen bonding to give a supramolecular framework. Springer Science+Business Media B.V. 2009.
Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof
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Paragraph 0055-0056; 0070; 0090; 0094; 0095; 0102, (2021/07/24)
The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.
Ultrasound-assisted, low-solvent and acid/base-free synthesis of 5-substituted 1,3,4-oxadiazole-2-thiols as potent antimicrobial and antioxidant agents
Yarmohammadi, Elahe,Beyzaei, Hamid,Aryan, Reza,Moradi, Ashraf
, p. 2367 - 2378 (2020/08/10)
Abstract: One of the goals of green chemistry is to use environmentally friendly solvents or remove and reduce the volume of harmful spent solvents. In this study, a novel process for the synthesis of 5-substituted 1,3,4-oxadiazole-2-thiol derivatives was proposed via ultrasound-assisted reaction of aryl hydrazides with CS2 (1:1 molar ratio) in some drops of DMF in the absence of basic or acidic catalysts. They were produced in good to excellent yields under easy workup and purification conditions. In order to prove the usefulness of the prepared compounds, their antioxidant, antibacterial, and antifungal potentials were screened by DPPH free radical scavenging, serial twofold microdilution and streak plate methods. Acceptable to significant inhibitory activities were observed with synthesized heterocycles. The results showed that 5-(4-fluorophenyl)-1,3,4-oxadiazole-2-thiol (3c) is an broad-spectrum antimicrobial agent. Many of them displayed remarkable antioxidant properties comparable to standard controls (ascorbic acid and α-tocopherol). Synthesized 1,3,4-oxadiazoles are also potent candidates to treat cancer, Parkinson, inflammatory, and diabetes diseases. Graphic Abstract: Eighteen 5-substituted 1,3,4-oxadiazole-2-thiol derivatives as potent antimicrobial and antioxidant agents were prepared via a new, efficient and green procedure.[Figure not available: see fulltext.].
Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker
Liu, Jie,Zhang, Guang-Yu,Zhang, Zhe,Li, Bo,Chai, Fei,Wang, Qi,Zhou, Zi-Dan,Xu, Ling-Ling,Wang, Shou-Kai,Jin, Zhen,Tang, You-Zhi
, (2021/05/17)
A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85–110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result of the time-kill curves displayed that compound 133 could inhibit the growth of MRSA in vitro quickly (- 4.36 log10 CFU/mL reduction). Then, compound 133 (- 1.82 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (- 0.82 log10 CFU/mL) in reducing MRSA load in mice thigh model. Besides, compound 133 exhibited low cytotoxicity to RAW 264.7 cells. Molecular docking studies revealed that compound 133 was successfully localized in the binding pocket of 50S ribosomal subunit (ΔGb = -10.50 kcal/mol). The results indicated that these pleuromutilin derivatives containing 1, 3, 4-oxadiazole might be further developed into novel antibiotics against MRSA.
Novel 1,3,4-oxadiazole compounds inhibit the tyrosinase and melanin level: Synthesis, in-vitro, and in-silico studies
Vanjare, Balasaheb D.,Choi, Nam Gyu,Mahajan, Prasad G.,Raza, Hussain,Hassan, Mubashir,Han, Yohan,Yu, Seon-Mi,Kim, Song Ja,Seo, Sung-Yum,Lee, Ki Hwan
, (2021/06/07)
In this research work, we have designed and synthesized some biologically useful of 1,3,4-Oxadiazoles. The structural interpretation of the synthesized compounds has been validated by using FT-IR, LC-MS, HRMS, 1H NMR and 13C NMR techniques. Moreover, the in-vitro mushroom tyrosinase inhibitory potential of the target compounds was assessed. The in-vitro study reveals that, all compounds demonstrate an excellent tyrosinase inhibitory activity. Especially, 2-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-ylthio)-N-phenylacetamide (IC50 = 0.003 ± 0.00 μM) confirms much more significant potent inhibition activity compared with standard drug kojic acid (IC50 = 16.83 ± 1.16 μM). Subsequently, the most potent five oxadiazole compounds were screened for cytotoxicity study against B16F10 melanoma cells using an MTT assay method. The survival rate for the most potent compound was more pleasant than other compounds. Furthermore, the western blot results proved that the most potent compound considerably decreased the expression level of tyrosinase at 50 μM (P 0.05). The molecular docking investigation exposed that the utmost potent compound displayed the significant interactions pattern within the active region of the tyrosinase enzyme and which might be responsible for the decent inhibitory activity towards the enzyme. A molecular dynamic simulation experiment was presented to recognize the residual backbone stability of protein structure.
Antibacterial and Antiviral Activities of 1,3,4-Oxadiazole Thioether 4H-Chromen-4-one Derivatives
Cao, Xiao,Liu, Fang,Liu, Liwei,Liu, Tingting,Peng, Feng,Wang, Qifan,Xie, Chengwei,Xue, Wei,Yang, Jinsong
, p. 11085 - 11094 (2021/10/01)
Various 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives were conceived. The title compounds demonstrated striking inhibitory effects againstXac,Psa, andXoo. EC50data exhibited that A8 (19.7 μg/mL) had better antibacterial activity againstXoothan myricetin, BT, and TC. Simultaneously, the mechanism of action of A8 had been verified by SEM. The results of anti-tobacco mosaic virus indicated that A9 had the bestin vivoantiviral effect compared with ningnanmycin. From the data of MST, it could be seen that A9 (0.003 ± 0.001 μmol/L) exhibited a strong binding capacity, which was far superior to ningnanmycin (2.726 ± 1.301 μmol/L). This study shows that the 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives may become agricultural drugs with great potential.
Development of Novel (+)-Nootkatone Thioethers Containing 1,3,4-Oxadiazole/Thiadiazole Moieties as Insecticide Candidates against Three Species of Insect Pests
Cheng, Wanqing,Fan, Jiangping,Guo, Yong,Han, Meiyue,Ma, Nannan,Yan, Xiaoting,Yang, Ruige
, p. 15544 - 15553 (2022/01/03)
To improve the insecticidal activity of (+)-nootkatone, a series of 42 (+)-nootkatone thioethers containing 1,3,4-oxadiazole/thiadiazole moieties were prepared to evaluate their insecticidal activities against Mythimna separata Walker, Myzus persicae Sulzer, and Plutella xylostella Linnaeus. Insecticidal evaluation revealed that most of the title derivatives exhibited more potent insecticidal activities than the precursor (+)-nootkatone after the introduction of 1,3,4-oxadiazole/thiadiazole on (+)-nootkatone. Among all of the (+)-nootkatone derivatives, compound 8c (1 mg/mL) exhibited the best growth inhibitory (GI) activity against M. separata with a final corrected mortality rate (CMR) of 71.4%, which was 1.54- and 1.43-fold that of (+)-nootkatone and toosendanin, respectively; 8c also displayed the most potent aphicidal activity against M. persicae with an LD50 value of 0.030 μg/larvae, which was closer to that of the commercial insecticidal etoxazole (0.026 μg/larvae); and 8s showed the best larvicidal activity against P. xylostella with an LC50 value of 0.27 mg/mL, which was 3.37-fold that of toosendanin and slightly higher than that of etoxazole (0.28 mg/mL). Furthermore, the control efficacy of 8s against P. xylostella in the pot experiments under greenhouse conditions was better than that of etoxazole. Structure-activity relationships (SARs) revealed that in most cases, the introduction of 1,3,4-oxadiazole/thiadiazole containing halophenyl groups at the C-13 position of (+)-nootkatone could obtain more active derivatives against M. separata, M. persicae, and P. xylostella than those containing other groups. In addition, toxicity assays indicated that these (+)-nootkatone derivatives had good selectivity to insects over nontarget organisms (normal mammalian NRK-52E cells and C. idella and N. denticulata fries) with relatively low toxicity. Therefore, the above results indicate that these (+)-nootkatone derivatives could be further explored as new lead compounds for the development of potential eco-friendly pesticides.
Efficient formation of C–S bond using heterocyclic thiones and arynes
An, Yu,Xu, Gang,Cai, Menglu,Wang, Shihui,Wang, Xiao zhong,Chen, Yingqi,Dai, Liyan
, (2020/12/23)
Phenylthio heterocyclic compounds are widely used because of their diverse biological activities and medicinal prospects. Here, a facile method was reported. An arylation of 1,3,4-oxa(thia)diazol-2-thiones reacting with arynes to build C(aryl)-S bonds in the presence of CsF had good yields and excellent selectivity. The reaction was completed in short time without using expensive reagents and catalysts. Present reaction system is an efficient procedure to process phenylthio heterocyclic compounds and reveals a sustainable method and better application prospects in future organic synthesis.
Synthesis and Biological Evaluation of Oxadiazole Clubbed Thiadiazole Derivatives as Antimicrobial Agents
Begari, Eeshwaraiah,Dave, Alpa Y.,Joshi, Deepkumar S.,Parmar, Kokila A.
, p. 273 - 280 (2021/08/03)
A series of 1,3,4-oxadiazole clubbed 1,3,4-thiadiazole derivatives were synthesized and assessed in vitro for their activity as antimicrobial agents. The target compounds 2-(5-(substituted aryl)-1, 3, 4-oxadiazol-2-ylthio)-N-(5-(substituted aryl)-1, 3, 4-thiadiazol-2-yl) acetamides (5a-5s) were synthesized using a basic condensation reaction between 5-(substituted aryl)-1,3,4-oxadiazole-2-thiol and 2-chloro-N-(5-(substituted aryl)-1,3,4-thiadiazol-2-yl)acetamide in presence of K2CO3 as a scavenging agent and acetone as reaction solvent. The titled compounds synthesized here, exhibited excellent to moderate antimicrobial activity against a broad panel of antibacterial strains of Gram-positive and Gram-negative bacteria and fungi.
