Design, synthesis, molecular docking and molecular dynamics studies of novel triazolothiadiazine derivatives containing furan or thiophene rings as anticancer agents

Osmaniye, Derya; Karaca, Şevval; Kurban, Berkant; Baysal, Merve; Ahmad, Iqrar; Patel, Harun; Özkay, Yusuf; Kaplancıklı, Zafer Asım

doi:10.1016/j.bioorg.2022.105709

Cited by 39 publications

(37 citation statements)

References 31 publications

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“…However, the average number of hydrogen bonds formed with the 1JIJ- 5d complex, 2HCK- 5d complex and 2QV4- 5d was 0.75, 0.20, and 0.34, respectively, which suggests that hydrogen bond formation events happen moderately with the 2HCK- 5d complex, and it may be stabilized by hydrophobic interaction as well as ionic interaction. Assessing the radius of gyration (RGyr), which may provide information on the system’s overall tightness, is another way of determining the root mean square distance of a collection of atoms from their common center of mass [ 56 , 57 ]. On analyzing the RGyr plot, we have interpreted that the RGyr values of the 1JIJ- 5d complex, 2HCK- 5d complex and 2QV4- 5d complex were 4.254 Å, 4.096 Å and 4.248 Å, respectively.…”

Section: Resultsmentioning

confidence: 99%

Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches

et al. 2022

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To combat emerging antimicrobial-resistant microbes, there is an urgent need to develop new antimicrobials with better therapeutic profiles. For this, a series of 13 new spiropyrrolidine derivatives were designed, synthesized, characterized and evaluated for their in vitro antimicrobial, antioxidant and antidiabetic potential. Antimicrobial results revealed that the designed compounds displayed good activity against clinical isolated strains, with 5d being the most potent (MIC 3.95 mM against Staphylococcus aureus ATCC 25923) compared to tetracycline (MIC 576.01 mM). The antioxidant activity was assessed by trapping DPPH, ABTS and FRAP assays. The results suggest remarkable antioxidant potential of all synthesized compounds, particularly 5c, exhibiting the strongest activity with IC50 of 3.26 ± 0.32 mM (DPPH), 7.03 ± 0.07 mM (ABTS) and 3.69 ± 0.72 mM (FRAP). Tested for their α-amylase inhibitory effect, the examined analogues display a variable degree of α-amylase activity with IC50 ranging between 0.55 ± 0.38 mM and 2.19 ± 0.23 mM compared to acarbose (IC50 1.19 ± 0.02 mM), with the most active compounds being 5d, followed by 5c and 5j, affording IC50 of 0.55 ± 0.38 mM, 0.92 ± 0.10 mM, and 0.95 ± 0.14 mM, respectively. Preliminary structure–activity relationships revealed the importance of such substituents in enhancing the activity. Furthermore, the ADME screening test was applied to optimize the physicochemical properties and determine their drug-like characteristics. Binding interactions and stability between ligands and active residues of the investigated enzymes were confirmed through molecular docking and dynamic simulation study. These findings provided guidance for further developing leading new spiropyrrolidine scaffolds with improved dual antimicrobial and antidiabetic activities.

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Section: Resultsmentioning

confidence: 99%

Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches

et al. 2022

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“…[20][21][22][23][24][25][26][27][28][29] So In our recent studies we unfolded our research to findings insides of synthesis and biological studies of thiophene derivatives. [30][31][32][33][34][35][36] A novel substituted thiophene analogues were designed, synthesized and screened for anticancer activity against U87-MG cell line. All these novel compounds are chemically synthesized in fewer steps.…”

Section: Introductionmentioning

confidence: 99%

“…Also there is lot of research on the medicinal significance of thiophen [20–29] . So In our recent studies we unfolded our research to findings insides of synthesis and biological studies of thiophene derivatives [30–36] . A novel substituted thiophene analogues were designed, synthesized and screened for anticancer activity against U87‐MG cell line.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, Molecular Docking and in vitro Anticancer Screening of Some Novel Thiophene Derivatives

Patel

et al. 2023

ChemistrySelect

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One of the diseases in the 21 st century is still cancer and there is significant research being done all over the world to find a medicine that is more effective and has fewer adverse effects. More than 19 million new cases of cancer have been reported by global statistics and an estimated 10 million people have died from it in 2020. We continue to work on the development of new pharmacological entities because we are motivated in the research area. We have created novel thiophene derivatives and have screened them against the U87-MG cell line to see whether they have any anticancer properties. It was observed that the AP-C12 extract showed the highest inhibition in the U87-MG cell line (EC 50 : 9.1 μM) which was a very good comparison to Temozolomide (EC 50 : 61.2 μM). Similarly, AP-C7 exhibited considerable potency against the U87-MG cell line with EC 50 values of 12.3 μM.

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“…Recently, Giampietro et al performed computational studies to design and prepare novel phenyldiazenyl sulfonamides and provided a sound rationale at a molecular level . In addition, Osmaniye et al used molecular docking and molecular dynamic studies to design and synthesize novel furan or thiophene ring containing triazolothiazine derivatives, which could have been used as anticancer agents . Moreover, these computational studies are important to save time and resources, whereby the expected outcomes are predicted theoretically rather than directly engaging with the experimental complications. , Machine learning as a subfield of computer science and statistics provides a platform for strong artificial intelligence and optimization concepts (delivering methods, theory, and domain of a wide range of applications), with the main focus on providing data to improve patient outcomes. − …”

Section: Introductionmentioning

confidence: 99%

Machine Learning-Assisted Prediction of the Biological Activity of Aromatase Inhibitors and Data Mining to Explore Similar Compounds

et al. 2022

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Designing molecules for drugs has been a hot topic for many decades. However, it is hard and expensive to find a new molecule. Thus, the cost of the final drug is also increased. Machine learning can provide the fastest way to predict the biological activity of druglike molecules. In the present work, machine learning models are trained for the prediction of the biological activity of aromatase inhibitors. Data was collected from the literature. Molecular descriptors are calculated to be used as independent features for model training. The results showed that the R 2 values for linear regression, random forest regression, gradient boosting regression, and bagging regression are 0.58, 0.84, 0.77, and 0.80, respectively. Using these models, it is possible to predict the activity of new molecules in a short period of time and at a reasonable cost. Furthermore, Tanimoto similarity is used for similarity analysis, as well as a chemical database is mined to search for similar molecules. Nonetheless, this study provides a framework for repurposing other effective drug molecules to prevent cancer.

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Design, synthesis, molecular docking and molecular dynamics studies of novel triazolothiadiazine derivatives containing furan or thiophene rings as anticancer agents

Cited by 39 publications

References 31 publications

Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches

Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches

Synthesis, Characterization, Molecular Docking and in vitro Anticancer Screening of Some Novel Thiophene Derivatives

Machine Learning-Assisted Prediction of the Biological Activity of Aromatase Inhibitors and Data Mining to Explore Similar Compounds

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