Synthesis and anticancer evaluation of new lipophilic 1,2,4 and 1,3,4-oxadiazoles

Caneschi, Wiliam; Enes, Karine Braga; Mendonça, Camille Carvalho de; Fernandes, Fábio de Souza; Miguel, Fábio Balbino; Martins, Jefferson da Silva; Hyaric, Mireille Le; Pinho, R.R.; Duarte, Lucas Mattos; Oliveira, Marcone Augusto Leal de; Santos, Hélio F. Dos; Lopes, Míriam Teresa Paz; Dittz, Dalton; Silva, Heveline; Couri, Mara R.C.

doi:10.1016/j.ejmech.2019.01.001

Cited by 47 publications

(24 citation statements)

References 35 publications

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“…Moreover, numerous literature reports have confirmed the multidirectional effect of the 1,3,4oxadiazole derivatives with the structure of N-Mannich bases [42][43][44][45][46]. Their anti-inflammatory activity is particularly worth noting [36,[47][48][49].…”

Section: Introductionmentioning

confidence: 90%

New 1,3,4-Oxadiazole Derivatives of Pyridothiazine-1,1-Dioxide with Anti-Inflammatory Activity

Glomb

Wiatrak

Gębczak

et al. 2020

IJMS

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Numerous studies have confirmed the coexistence of oxidative stress and inflammatory processes. Long-term inflammation and oxidative stress may significantly affect the initiation of the neoplastic transformation process. Here, we describe the synthesis of a new series of Mannich base-type hybrid compounds containing an arylpiperazine residue, 1,3,4-oxadiazole ring, and pyridothiazine-1,1-dioxide core. The synthesis was carried out with the hope that the hybridization of different pharmacophoric molecules would result in a synergistic effect on their anti-inflammatory activity, especially the ability to inhibit cyclooxygenase. The obtained compounds were investigated in terms of their potencies to inhibit cyclooxygenase COX-1 and COX-2 enzymes with the use of the colorimetric inhibitor screening assay. Their antioxidant and cytotoxic effect on normal human dermal fibroblasts (NHDF) was also studied. Strong COX-2 inhibitory activity was observed after the use of TG6 and, especially, TG4. The TG11 compound, as well as reference meloxicam, turned out to be a preferential COX-2 inhibitor. TG12 was, in turn, a non-selective COX inhibitor. A molecular docking study was performed to understand the binding interaction of compounds at the active site of cyclooxygenases.

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Section: Introductionmentioning

confidence: 90%

New 1,3,4-Oxadiazole Derivatives of Pyridothiazine-1,1-Dioxide with Anti-Inflammatory Activity

Glomb

Wiatrak

Gębczak

et al. 2020

IJMS

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show abstract

“…1,3,4‐Oxadiazole replaced by 1,3,4‐thiadiazole showed potent telomerase activity ( 22 , IC 50 = 1.2 μM), 5‐(quinolin‐2‐yl)‐1,3,4‐oxadiazole derivatives also exhibited similar inhibitory activity ( 23 , IC 50 = 0.8 μM) . Compound 24 showed to be capable to induce apoptosis in 4T1 and CT26, a crucial cellular process for effective chemotherapeutic agents, and compound 25 caused apoptotic morphological changes in both cell lines obtained from micrographs by transmission electron microscopy …”

Section: Small Molecule Inhibitorsmentioning

confidence: 99%

Therapeutic strategies for targeting telomerase in cancer

Chen

Tang

Shi

et al. 2019

Medicinal Research Reviews

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Telomere and telomerase play important roles in abnormal cell proliferation, metastasis, stem cell maintenance, and immortalization in various cancers. Therefore, designing of drugs targeting telomerase and telomere is of great significance. Over the past two decades, considerable knowledge regarding telomere and telomerase has been accumulated, which provides theoretical support for the design of therapeutic strategies such as telomere elongation. Therefore, the development of telomere‐based therapies such as nucleoside analogs, non‐nucleoside small molecules, antisense technology, ribozymes, and dominant negative human telomerase reverse transcriptase are being prioritized for eradicating a majority of tumors. While the benefits of telomere‐based therapies are obvious, there is a need to address the limitations of various therapeutic strategies to improve the possibility of clinical applications. In this study, current knowledge of telomere and telomerase is discussed, and therapeutic strategies based on recent research are reviewed.

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“…Docking results of the designed ligands (L1-L20) and control. [34,35,36,37,38]. The interactions of ligand L10 and control with the functional residues of 6WUU were studied using the Ligplotþ program and are depicted in Figure 5 (a) and (b) respectively.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

Structure-based drug designing of naphthalene based SARS-CoV PLpro inhibitors for the treatment of COVID-19

Bhati¹

2020

Heliyon

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The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a greater challenge for the world. Coronavirus has infected over 38.3 million people and caused millions of deaths worldwide. The COVID-19 outbreak has accentuated the need for additional efforts to develop broad-spectrum therapeutics to combat SARS-CoV-2 infection. In the current investigation, an attempt was made to design potential SARS-CoV PLpro inhibitors containing naphthalene and 3,4-dihydro-2H-pyran moieties connected via-NHCO-linker. The ligands obeyed Lipinski's rule and were found to have good drug-likeness and ADMET properties. Docking simulations confirmed strong binding affinity and inhibition potential of the designed ligands against the receptor SARS CoV-2 Papain-like protease (PLpro). LigandL10 incorporating the oxadiazole ring system displayed better binding affinity than the control 5-acetamido-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide. Further, the docked complex of LigandL10 was subjected to molecular dynamics (MD) simulation to examine the molecular mechanisms of protein-ligand interactions. The results of the present study are encouraging. Ligand L10 emerged as the most potent ligand in the series and could be considered for further research for the development of potential therapeutics for the treatment of COVID-19.

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Synthesis and anticancer evaluation of new lipophilic 1,2,4 and 1,3,4-oxadiazoles

Cited by 47 publications

References 35 publications

New 1,3,4-Oxadiazole Derivatives of Pyridothiazine-1,1-Dioxide with Anti-Inflammatory Activity

New 1,3,4-Oxadiazole Derivatives of Pyridothiazine-1,1-Dioxide with Anti-Inflammatory Activity

Therapeutic strategies for targeting telomerase in cancer

Structure-based drug designing of naphthalene based SARS-CoV PLpro inhibitors for the treatment of COVID-19

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