3291-03-0Relevant articles and documents
LASSBio-1586, an N-acylhydrazone derivative, attenuates nociceptive behavior and the inflammatory response in mice
Silva, Juliane Cabral,De Oliveira, Raimundo Gon?alves,e Silva, Mariana Gama,De Lavor, érica Martins,Soares, Juliana Mikaelly Dias,De Lima-Saraiva, Sarah Raquel Gomes,Diniz, Tamara Coimbra,Mendes, Rosemairy Luciane,De Alencar Filho, Edilson Beserra,De Lacerda Barreiro, Eliezer Jesus,Lima, Lídia Moreira,Da Silva Almeida, Jackson Roberto Guedes
, (2018)
Pain and inflammation are complex clinical conditions that are present in a wide variety of disorders. Most drugs used to treat pain and inflammation have potential side effects, which makes it necessary to search for new sources of bioactive molecules. In this paper, we describe the ability of LASSBio-1586, an N-acylhydrazone derivative, to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In these experimental models, LASSBio-1586 significantly (p0.05) reduced nociceptive behavior. Several methods of acute and chronic inflammation induced by different chemical (carrageenan, histamine, croton oil, arachidonic acid) and physical (cotton pellet) agents were used to evaluate the anti-inflammatory effect of LASSBio-1586. LASSBio-1586 exhibited potent anti-inflammatory activity in all tests (p0.05). Study of the mechanism of action demonstrated the possible involvement of the nitrergic, serotonergic and histamine signaling pathways. In addition, a molecular docking study was performed, indicating that LASSBio-1586 is able to block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. In summary, LASSBio-1586 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.
Synthesis, characterization (theoretical and biological study) of some transition metal complexes with new schiff base derived from 1,2,4-triazole
AL-Jibouri, Mahmoud Najim,Jawad, Waleed A.,Balakit, Asim A.,Obies, Mohammed
, p. 5229 - 5241 (2021/08/31)
The present work involves, new Schiff base of (E)-2-(((3-mercapto-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazol-4-yl)imino)methyl)phenol (L2) has been synthesized by condensation reaction of 4-amino-5-(3,4,5 trimethoxy phenyl)-4H-1,2,4-triazole-3-thiol with 2-hydroxybenzaldehyde. The new Schiff base (L2) used as a ligand to synthesize a new complex with Co(II), Ni(II), Cu(II), Pd(II), and Cd(II) metal ions by 1:1 (Metal: ligand) ratio. New ligand and their complexes have been exanimated and confirmed by fourier-transform infrared (FT-IR), ultraviolet-visible (UV-visible), proton nuclear magnetic resonance (1HNMR), carbon13 nuclear magnetic resonance (13CNMR), microelement analysis (CHNS), thermal analysis (TG-DSC), atomic absorption flame (AAF), conductivity and magnetic susceptibility. The results obtained from spectra, elemental analyses and thermal analyses (TG-DSC) and compare by density functional theory (DFT) and TD-DFT calculations were screened for some selected complexes and the observed data indicated their stability and the expected chemical formula, Pd(II) were square planner, whereas the Cu(II), Co(II), Ni(II) octahedral, and Cd(II) were tetrahedral geometry . Furthermore, the antibacterial and antifungal activity was screened for the DMSO solution concerning the Schiff base (L2) and its complexes (20 μg/ml) against two kinds of gram; (Staphylococcus aureas and Bacillus subtilis) positive and two negative bacteria; (Esherichia coli and Burkholderia) and against (Candida albican) fungi. The results obtained from diffusion method confirmed the greater activity of Pd(II) and Cd(II) complexes whereas the Co(II),Cu(II) and Ni(II) complexes showed medium activity compared with the low inhibition zones of the free Schiff base of 1, 2, 4- triazole derivative.
Molecular docking studies, biological evaluation and synthesis of novel 3-mercapto-1,2,4-triazole derivatives
Ghanaat, Javad,Khalilzadeh, Mohammad A.,Zareyee, Daryoush
, p. 223 - 232 (2020/02/25)
Abstract: Synthesis of bioactive heterocyclic compounds having effective biological activity is an essential research area for wide-ranging applications. In this study, a conventional methodology has been developed for the synthesis of a series of new 3-mercapto-1,2,4-triazole derivatives 4a–f. The purity and structure of the synthesized molecules were confirmed by 1H NMR, 13C NMR and elemental analysis. In addition, the prepared compounds were screened for their anti-proliferative activity against three human cancer cell lines including A549 (lung cancer), MCF7 (breast cancer) and SKOV3 (ovarian cancer) using MTT reduction assay. All the tested compounds demonstrated remarkable cytotoxic activity with IC50 values ranging from 3.02 to 15.37?μM. The heterocyclic compound bearing 3,4,5-trimethoxy moiety was found to be the most effective among the series displaying an IC50 of 3.02?μM specifically against the ovarian carcinoma cancer cell line (SKOV3). Moreover, Annexin V-FITC/propidium iodide staining assay indicated that this compound can induce apoptosis in SKOV3 cells. Furthermore, cell cycle assay showed a significant cell cycle arrest at the G2/M phase in a dose-dependent manner for this compound. The molecular docking results was showed binding modes of potent compound 4d perfectly corroborated the suggestion of binding to the colchicine site. The entire results conclude that 3-mercapto-1,2,4-triazole derivatives can be synthesized by a green method for biological and pharmacological applications. Graphic abstract: New analogs of 3-mercapto-1,2,4-triazole potential derivatives for anti-proliferative activity were synthesized. Cytotoxic activity of all synthesized compounds was evaluated against tree human cancer cell lines: lung (A549), breast (MCF7) and ovarian (SKOV3).[Figure not available: see fulltext.].
Design, synthesis, and biological evaluation of phenyloxadiazole derivatives as potential antifungal agents against phytopathogenic fungi
Li, Yitao,Yao, Wenqiang,Lin, Jian,Gao, Guoliang,Huang, Chang,Wu, Yang
, p. 121 - 135 (2021/01/05)
Abstract: A novel series of picarbutrazox-inspired oxadiazole hybrids was synthesized and the derivatives’ biological activity against phytopathogenic fungi was investigated. The molecules were designed by retaining the active fragment of tetrazolyl phenyloxime ether of lead compound picarbutrazox, while introducing the potentially active oxadiazole-derived fragment. Bioassay results revealed that some of the title compounds showed potent in vivo antifungal activities to control cucumber downy mildew. Therefore, this novel oxadiazole phenyloxadiazole derivative can be used as a potential antifungal agent to control cucumber downy mildew and other phytopathogenic fungi for crop protection. Graphic abstract: [Figure not available: see fulltext.].
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.
Synthesis, biological evaluation, and structure-activity relationships of new tubulin polymerization inhibitors based on 5-amino-1,2,4-triazole scaffold
Yang, Fang,Chen, Lin,Lai, Jin-Mei,Jian, Xie-Er,Lv, Dong-Xin,Yuan, Li-Li,Liu, Yu-Xia,Liang, Feng-Ting,Zheng, Xiao-Lan,Li, Xiong-Li,Wei, Li-Yuan,You, Wen-Wei,Zhao, Pei-Liang
, (2021/03/06)
Based on our previous research, thirty new 5-amino-1H-1,2,4-triazoles possessing 3,4,5-trimethoxyphenyl moiety were synthesized, and evaluated for antiproliferative activities. Among them, compounds IIa, IIIh, and IIIm demonstrated significant antiproliferative activities against a panel of tumor cell lines, and the promising compound IIIm dose-dependently caused G2/M phase arrest in HeLa cells. Furthermore, analogue IIa exhibited the most potent tubulin polymerization inhibitory activity with an IC50 value of 9.4 μM, and molecular modeling studies revealed that IIa formed stable interactions in the colchicine-binding site of tubulin, suggesting that 5-amino-1H-1,2,4-triazole scaffold has potential for further investigation to develop novel tubulin polymerization inhibitors with anticancer activity.
Discovery of highly potent tubulin polymerization inhibitors: Design, synthesis, and structure-activity relationships of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines
Huo, Xian-Sen,Jian, Xie-Er,Ou-Yang, Jie,Chen, Lin,Yang, Fang,Lv, Dong-Xin,You, Wen-Wei,Rao, Jin-Jun,Zhao, Pei-Liang
, (2021/05/10)
By removing 5-methyl and 6-acetyl groups in our previously reported compound 3, we designed a series of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential tubulin polymerization inhibitors. Among them, compound 5e displayed low nanomolar antiproliferative efficacy on HeLa cells which was 166-fold higher than the lead analogue 3. Interestingly, 5e displayed significant selectivity in inhibiting cancer cells over HEK-293 (normal human embryonic kidney cells). In addition, 5e dose-dependently arrested HeLa in G2/M phase through the alterations of the expression levels of p-cdc2 and cyclin B1, and caused HeLa cells apoptosis by regulation of expressions of cleaved PARP. Further evidence demonstrated that 5e effectively inhibited tubulin polymerization and was 3-fold more powerful than positive control CA-4. Moreover, molecular docking analysis indicated that 5e overlapped well with CA-4 in the colchicine-binding site. These studies demonstrated that 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine skeleton might be used as the leading unit to develop novel tubulin polymerization inhibitors as potential anticancer agents.
Design, Synthesis, and Pharmacological Evaluation of First-in-Class Multitarget N-Acylhydrazone Derivatives as Selective HDAC6/8 and PI3Kα Inhibitors
Alves, Marina A.,Chaves, Lorrane S.,Fernandes, Patrícia D.,Fraga, Carlos A. M.,Guerra, Fabiana S.,Rodrigues, Daniel A.,Sagrillo, Fernanda S.,Sant'Anna, Carlos M. R.,Thota, Sreekanth,de Sena M. Pinheiro, Pedro
supporting information, (2020/02/25)
Targeting histone deacetylases (HDACs) and phosphatidylinositol 3-kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N-acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kα dual inhibitors. The surprising selectivity for PI3Kα may be related to differences in the conformation in the active site. Cellular studies showed that these compounds act in HDAC6 inhibition and the PI3/K/AKT/mTOR pathway. The compounds that are selective for inhibition of HDAC6/8 and inhibit PI3Kα show potential for the treatment of cancer.
Tubulin inhibitors: Discovery of a new scaffold targeting extra-binding residues within the colchicine site through anchoring substituents properly adapted to their pocket by a semi-flexible linker
AbdelHafez, El-Shimaa M. N.,Abdelhamid, Dalia,Aly, Omar M.,Maklad, Raed M.
supporting information, (2020/04/22)
Bis-hydrazides 13a-h were designed and synthesized as potential tubulin inhibitors selectively targeting the colchicine site between α- and β-tubulin subunits. The newly designed ring-B substituents were assisted at their ends by ‘a(chǎn)nchor groups’ which are expected to exert binding interaction(s) with new additional amino acid residues in the colchicine site (beyond those amino acids previously reported to interact with reference inhibitors as CA-4 and colchicine). Conformational flexibility of bis-hydrazide linker assisted these ‘extra-binding’ properties through reliving ligands’ strains in the final ligand-receptor complexes. Compound 13f displayed the most promising computational and biological study results in the series: MM/GBSA binding energy of ?62.362 kcal/mol (extra-binding to Arg α:221, Thr β:353 & Lys β:254); 34% NCI-H522 cells’ death (at 10 μM), IC50 = 0.073 μM (MTT assay); significant cell cycle arrest at G2/M phase; 11.6% preG1 apoptosis induction and 83.1% in vitro tubulin inhibition (at concentration = IC50). Future researchers in bis-hydrazide tubulin inhibitors are advised to consider the 2-chloro-N-(4-substituted-phenyl)acetamide derivatives as compound 13f due to extra-binding properties of their ring B.
Cell cycle inhibition, apoptosis, and molecular docking studies of the novel anticancer bioactive 1,2,4-triazole derivatives
Ghanaat, Javad,Khalilzadeh, Mohammad A.,Zareyee, Daryoush,Shokouhimehr, Mohammadreza,Varma, Rajender S.
, p. 691 - 699 (2019/12/12)
Several 3-alkylsulfanyl-1,2,4-triazole derivatives were synthesized and their relevant structures confirmed based on their elemental analysis and nuclear magnetic resonance. The anticancer activity of all the derivatives was evaluated for A549, MCF7, and SKOV3 cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay wherein compound 5e demonstrated significant anti-proliferative activities against all cell lines whereas 5b and 5e showed efficient anti-proliferative actions in SKOV3 cell line having half maximal inhibitory concentration (IC50) values of 0.81 and 0.53 μM, respectively. Furthermore, compound 5e was found to drive remarkable cell cycle arrest at the G2/M phase for SKOV3 cell lines in a concentration-dependent behavior. Molecular docking studies performed with these derivatives validated them as appropriate candidates for further studies of their potential anticancer activity.
