Corrigendum to “Rational design-aided discovery of novel 1,2,4-oxadiazole derivatives as potential EGFR inhibitors” [Bioorg. Chem. 114 (2021) 105124]

Unadkat, Vishal; Rohit, Shishir; Parikh, Paranjay; Sanna, Vinod K.; Singh, Sanjay; Patel, Kaushal P.

doi:10.1016/j.bioorg.2021.105459

Cited by 4 publications

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“…In comparison to the reference doxorubicin, the assay findings demonstrated a promising antiproliferative effect against a panel of cancer cell lines, with low micromolar IC 50 values against EGFR. [49] HENDAWY | 5 of 14…”

Section: Antitumor Agentsmentioning

confidence: 99%

A comprehensive review of recent advances in the biological activities of 1,2,4‐oxadiazoles

Hendawy

2022

Archiv der Pharmazie

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Nitrogen heterocycles play an essential role in medication development. The 1,2,4‐oxadiazole heterocycle has been extensively studied, yielding a large variety of molecules with varied biological functions. The 1,2,4‐oxadiazole shows bioisosteric equivalency with ester and amide moieties. In recent years, the 1,2,4‐oxadiazole nucleus has received a lot of attention in medicinal chemistry. It was thought to be a pharmacophore component in the production of biologically intriguing drugs. This review presents a comprehensive overview of the recent achievements in the biological activities of 1,2,4‐oxadiazoles as potential antimicrobial, anticancer, anti‐inflammatory, neuroprotective, and antidiabetic agents. The structure–activity relationship and mechanisms of action are also reviewed.

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Section: Antitumor Agentsmentioning

confidence: 99%

A comprehensive review of recent advances in the biological activities of 1,2,4‐oxadiazoles

Hendawy

2022

Archiv der Pharmazie

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“…On the other hand, many oxadiazole derivatives are known to possess a wide range of bioactivities such as antibacterial, [22] antitubercular, [23] anti‐inflammatory, [24] antitrypanosomal, [25] antioxidant, [26] anticonvulsant, [27] anticancer, [28] EGFR [29] and carbonic anhydrase [30] inhibitors.…”

Section: Introductionmentioning

confidence: 99%

“…Increasing interest towards the benzimidazole ring system has been observed as it is the basis for the development of many compounds with a diversity of biological activities such as antibacterial, [9] antimicrobial, [10] antifungal, [11] antioxidant, [12] anticancer, [13] anti-inflammatory, [14] antiprotozoal, [15] antiviral, [16] antidiabetic, [17] antihypertensive, [18] antimycobacterial, [19] antithrombin [20] and tubulin inhibitor. [21] On the other hand, many oxadiazole derivatives are known to possess a wide range of bioactivities such as antibacterial, [22] antitubercular, [23] anti-inflammatory, [24] antitrypanosomal, [25] antioxidant, [26] anticonvulsant, [27] anticancer, [28] EGFR [29] and carbonic anhydrase [30] inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, in Vitro and in Silico Studies of Benzimidazole‐Linked Oxadiazole Derivatives as Anti‐inflammatory Agents

et al. 2022

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In this study, 24 new benzimidazole‐oxadiazole hybrids were designed and synthesized as anti‐inflammatory agents. It was measured their stabilizing potentials against heat‐induced human erythrocyte membrane hemolysis for anti‐inflammatory activity. Compound 5 w bearing cyclohexyl as R2 group at the 2nd position of oxadiazole ring and 3,4‐dimethoxy phenyl at the 2nd position of benzimidazole showed the highest membrane stabilizing activity with IC50= 0.50 mM. Antioxidant activity screening of compounds synthesized by ABTS and DPPH radical scavenging assay methods was performed. Molecular docking studies of all compounds were performed against COX‐1 and COX‐2 with Glide XP. Moreover, to examine the protein‐ligand stability of the most active compound 5 w, molecular dynamics simulations of 100 ns duration were performed with COX‐1 and COX‐2 using Gromacs.

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“…Our previous study screened a library of heterocyclic molecules and identified a set of fourteen molecules exhibiting EGFR inhibition. 24 , 25 In this study, we have performed a molecular docking study on all the fourteen compounds that revealed the four most active compounds/molecules. Finally, these four compounds were chosen for molecular dynamics study and ADME profiling to understand their drug-like properties.…”

Section: Introductionmentioning

confidence: 99%

Identification of 1,2,4-Oxadiazoles-Based Novel EGFR Inhibitors: Molecular Dynamics Simulation-Guided Identification and in vitro ADME Studies

Unadkat¹,

Rohit²,

Parikh³

et al. 2022

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Background In this work, we have identified heterocyclic derivatives with 1,2,4 oxadiazole scaffold mimicking the functions of tyrosine kinase inhibitors. Fourteen molecules that displayed the best fit were picked from the library of compounds and studied under in-silico and in-vitro conditions. Four compounds were selected for further cytotoxicity and ADME (Absorption, Distribution, Metabolism, Elimination) profiling showing IC 50 (from 8–13 µM) values against EGFR positive cancer cell line (MCF7). Methods A molecular dynamics simulation study was performed to understand the correlation of non-covalent binding energies with biological activity. The drug-like properties of the selected four compounds (7a, 7b, 7e, and 7m) were evaluated by in-vitro ADME studies. Compounds 7a, 7b , and 7m were the active compounds in the molecular dynamics simulations study. Further, EGFR binding activity was confirmed with EGFR WT and EGFR T790M kinase assay using a luminescence-based method. Results These compounds ( 7a, 7b , and 7m ) showed activity against EGFR WT and mutant EGFR T790M , exhibiting IC 50 values of <10 and <50 micromolar, respectively. These compounds also possess moderate aqueous solubility in 40–70 µg/mL at pH 7.4 and 30–100 µg/mL at pH 4.0. Further, 7a, 7b , and 7m showed balanced lipophilicity with Log D values ranging from 1–3. They demonstrated a good correlation in Caco-2 permeability with Apparent permeability (Papp) 1 to 5 × 10 −6 cm/s in comparison with 7e , which was found to be highly lipophilic (Log D >5) and showed high permeability (Papp 17 × 10 −6 cm/s). Lastly, all these compounds were moderately stable in liver microsomes at alkaline pH with a half-life of 30–60 min, while at a highly acidic pH (2.0), the compounds were stable up to 15–20 min. Conclusion Overall, in-vitro ADME results of these molecules showed good drug-like properties, which are well correlated with the in-silico ADME data, making them ideal for developing an oral drug delivery formulation.

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Corrigendum to “Rational design-aided discovery of novel 1,2,4-oxadiazole derivatives as potential EGFR inhibitors” [Bioorg. Chem. 114 (2021) 105124]

Cited by 4 publications

References 0 publications

A comprehensive review of recent advances in the biological activities of 1,2,4‐oxadiazoles

A comprehensive review of recent advances in the biological activities of 1,2,4‐oxadiazoles

Design, Synthesis, in Vitro and in Silico Studies of Benzimidazole‐Linked Oxadiazole Derivatives as Anti‐inflammatory Agents

Identification of 1,2,4-Oxadiazoles-Based Novel EGFR Inhibitors: Molecular Dynamics Simulation-Guided Identification and in vitro ADME Studies

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