scholarly journals QSAR Model of Indeno[1,2-b]indole Derivatives and Identification of N-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-b]furan-3-carboxamide as a Potent CK2 Inhibitor

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 97 ◽  
Author(s):  
Samer Haidar ◽  
Christelle Marminon ◽  
Dagmar Aichele ◽  
Abdelhamid Nacereddine ◽  
Wael Zeinyeh ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Qsar Model ◽  
Biological Evaluation ◽  
Indole Derivatives ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Synthesis And Biological Evaluation ◽  
Ck2 Inhibitors ◽  
Ck2 Inhibitor

Casein kinase II (CK2) is an intensively studied enzyme, involved in different diseases, cancer in particular. Different scaffolds were used to develop inhibitors of this enzyme. Here, we report on the synthesis and biological evaluation of twenty phenolic, ketonic, and para-quinonic indeno[1,2-b]indole derivatives as CK2 inhibitors. The most active compounds were 5-isopropyl-1-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4h and 1,3-dibromo-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4w with identical IC50 values of 0.11 µM. Furthermore, the development of a QSAR model based on the structure of indeno[1,2-b]indoles was performed. This model was used to predict the activity of 25 compounds with naphtho[2,3-b]furan-4,9-dione derivatives, which were previously predicted as CK2 inhibitors via a molecular modeling approach. The activities of four naphtho[2,3-b]furan-4,9-dione derivatives were determined in vitro and one of them (N-isopentyl-2-methyl-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-3-carboxamide) turned out to inhibit CK2 with an IC50 value of 2.33 µM. All four candidates were able to reduce the cell viability by more than 60% after 24 h of incubation using 10 µM.

Synthesis and Biological Evaluation of Novel 4-Phenylaminobenzofuro[2,3-d]pyrimidine Derivatives

2020 ◽  
Vol 42 (4) ◽  
pp. 564-564
Author(s):  
Ju liu Ju liu ◽  
Jun Li Jun Li ◽  
Jian tao Shi Jian tao Shi ◽  
Jie Li Jie Li ◽  
Xue chen Hao Xue chen Hao ◽  
...  
Keyword(s):  
Cell Lines ◽  
A549 Cells ◽  
Positive Control ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Pyrimidine Derivatives ◽  
Concentration Dependent Manner ◽  
Ic50 Value ◽  
Synthesis And Biological Evaluation

A series of novel 4-phenylaminobenzofuro[2,3-d]pyrimidine derivatives had been prepared and assessed for their in vitro antiproliferative activities against three lung cancer cell lines (A549, H460 and H1975). The bioassay results showed most of the designed compounds exhibited potential antiproliferation activities. Among them, compound 8f exhibited remarkable inhibitory activity against A549 and H460 cell lines with IC50 value of 2.54 μM and 2.68 μM, respectively, which was comparable to that of the positive control sorafenib (IC50 = 2.69 μM for A549 and 3.71 μM for H460). AO/EB staining suggests that compound 8f could induce apoptosis in A549 cells. Furthermore, cell cycle analyses show that compound 8f increased G0/G1 A549 cells arrest in a concentration-dependent manner. The preliminary structure-activity relationships (SARs) studies indicated that mono-electron-withdrawing groups (mono-EWGs) on the phenyl ring are positive on the antitumor activity.

scholarly journals Synthesis and biological evaluation of 2-(4-methylsulfonyl phenyl) indole derivatives: Multi-target compounds with dual antimicrobial and anti-inflammatory activities

2020 ◽  
Author(s):  
Ahmed Shaker ◽  
Eman K. A. Abdelall ◽  
Khaled R. A. Abdellatif ◽  
Hamdy M. Abdel-Rahman
Keyword(s):  
Active Site ◽  
High Selectivity ◽  
Biological Evaluation ◽  
Indole Derivatives ◽  
E Coli ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Synthesis And Biological Evaluation

Abstract Three series of 2-(4-methylsulfonylphenyl) indole derivatives have been designed and synthesized. The synthesized compounds were evaluated for their antimicrobial, COX inhibitory and anti-inflammatory activities. Compound 7g was identified to be the most potent antibacterial candidate against strains of MRSA , E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii , respectively with safe therapeutic dose. Compounds 7a-k, 8a-c and 9a-c showed good anti-inflammatory activity with high selectivity toward COX-2 in comparison with reference drugs indomethacin and celecoxib. Compounds 9a-c were found to release moderate amounts of NO to decrease the side effects associated with selective COX-2 inhibitors. A molecular modeling study for compounds 7b, 7h, and 7i into COX-2 active site correlated with results of in vitro COX-2 inhibition assays.

scholarly journals Synthesis and biological evaluation of 2-(4-methylsulfonyl phenyl) indole derivatives: Multi-target compounds with dual antimicrobial and anti-inflammatory activities

2019 ◽  
Author(s):  
Ahmed Shaker ◽  
Eman K. A. Abdelall ◽  
Khaled R. A. Abdellatif ◽  
Hamdy M. Abdel-Rahman
Keyword(s):  
Active Site ◽  
High Selectivity ◽  
Biological Evaluation ◽  
Indole Derivatives ◽  
E Coli ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Synthesis And Biological Evaluation

Abstract Three series of 2-(4-methylsulfonylphenyl) indole derivatives have been designed and synthesized. The synthesized compounds were evaluated for their antimicrobial, COX inhibitory and anti-inflammatory activities. Compound 7g was identified to be the most potent antibacterial candidate against strains of MRSA , E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii , respectively with safe therapeutic dose. Compounds 7a-k, 8a-c and 9a-c showed good anti-inflammatory activity with high selectivity toward COX-2 in comparison with reference drugs indomethacin and celecoxib. Compounds 9a-c were found to release moderate amounts of NO to decrease the side effects associated with selective COX-2 inhibitors. A molecular modeling study for compounds 7b, 7h, and 7i into COX-2 active site correlated with results of in vitro COX-2 inhibition assays.

scholarly journals Synthesis and Biological Evaluation of 2-methyl-1Hbenzimidazole and 1H-benzimidazol-2-yl-methanol

2016 ◽  
Vol 15 (1) ◽  
pp. 83-87 ◽  
Author(s):  
Saikat Kumar Poddar ◽  
Nazmus Saqueeb ◽  
SM Abdur Rahman
Keyword(s):  
Antioxidant Activity ◽  
Biological Evaluation ◽  
Benzimidazole Derivatives ◽  
Cytotoxic Activities ◽  
Lc50 Value ◽  
Ic50 Value ◽  
Vincristine Sulphate ◽  
Ic50 Values ◽  
High Yields ◽  
Synthesis And Biological Evaluation

Two benzimidazole derivatives namely 2-methyl-1H-benzimidazole (1) and 1H-benzimidazol-2- ylmethanol (2) were synthesized in high yields by condensing O-phenylenediamine with two different carboxylic acid derivatives: glacial acetic acid and glycolic acid, following a different synthetic protocol. Structures were elucidated by spectroscopic methods. Among the two benzimidazole derivatives synthesized, 2-methyl-1Hbenzimidazole (1) showed moderate antioxidant activity with IC50 values of 144.84?g/ml whereas 1H-benzimidazol- 2-ylmethanol (2) displayed mild antioxidant activity (IC50 value 400.42 ?g/ml). Compound 1 also exhibited prominent cytotoxic activities with the LC50 value of 0.42 ?g/ml when compared to the standard vincristine sulphate (LC50 value of 0.544 ?g/ ml). It also demonstrated weak antimicrobial activity having 7-8 mm of zone of inhibition.Dhaka Univ. J. Pharm. Sci. 15(1): 83-87, 2016 (June)

Synthesis and Molecular Modeling of Novel 3,5-Bis(trifluoromethyl)benzylamino Benzamides as Potential CETP Inhibitors

2021 ◽  
Vol 17 ◽  
Author(s):  
Reema Abu Khalaf ◽  
Mohammad Awad ◽  
Tariq Al-Qirim ◽  
Dima Sabbah
Keyword(s):  
Molecular Modeling ◽  
Cholesteryl Ester ◽  
Hdl Cholesterol ◽  
Biological Evaluation ◽  
Lead Compounds ◽  
Transfer Protein ◽  
Cetp Inhibitors ◽  
Good Target ◽  
Ic50 Values

Background: There is an alarming spread of cases of lipid-disorders in the world that occur due to harmful lifestyle habits, hereditary risk influences, or as a result of other illnesses or medicines. Cholesteryl ester transfer protein (CETP) is a 476-residue lipophilic glycoprotein that helps in the transport of cholesteryl ester and phospholipids from the atheroprotective HDL to the proatherogenic LDL and VLDL. Inhibition of CETP leads to elevation of HDL cholesterol and reduction of LDL cholesterol and triglycerides, so it's considered a good target for the treatment of hyperlipidemia and its comorbidities. Objectives: In this research synthesis, characterization, molecular modeling and biological evaluation of eight 3,5-bis(trifluoromethyl)benzylamino benzamides 9a-d and 10a-d were carried out. Methods: The synthesized molecules were characterized using 1H-NMR, 13C-NMR, IR and HR-MS. They were in vitro biologically tested to estimate their CETP inhibitory activity. Results: These compounds offered inhibitory effectiveness ranging from 42.2% to 100% at a concentration of 10 µM. Compounds bearing unsubstituted three aromatic rings (9a) or ortho-CF3 substituted (9b) were the most effective compounds among their analogs and showed IC50 values of 1.36 and 0.69 μM, respectively. The high docking scores of 9a-d and 10a-d against 4EWS imply that they might be possible CETP inhibitors. Pharmacophore mapping results demonstrate that the series approves the fingerprint of CETP active inhibitors and therefore explains their high binding affinity against CETP binding site. Conclusion: This work concludes that 3,5-bis(trifluoromethyl)benzylamino benzamides can serve as a promising CETP inhibitors lead compounds.

scholarly journals Synthesis and Biological Evaluation of Analogs of Didehydroepiandrosterone as Potential New Anticancer Agents

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3052
Author(s):  
Eirik J. Solum ◽  
Sandra Liekens ◽  
Trond Vidar Hansen
Keyword(s):  
Endothelial Cell ◽  
Anticancer Agents ◽  
Biological Evaluation ◽  
Side Chain ◽  
Microvascular Endothelial Cell ◽  
Reference Standard ◽  
Cytotoxic Effects ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Synthesis And Biological Evaluation

The synthesis, cytotoxicity and inhibition of CDK8 by thirteen analogs of cortistatin A are reported. These efforts revealed that the analogs with either a 6- or 7-isoquinoline or 5-indole side chain in the 17-position are the most promising anti-proliferative agents. These compounds showed potent cytotoxic effects in CEM, HeLa and HMEC-1 cells. All three compounds exhibited IC50 values < 10µM. The most interesting 10l analog exhibited an IC50 value of 0.59 µM towards the human dermal microvascular endothelial cell line (HMEC-1), significantly lower than the reference standard 2-methoxyestradiol. At a concentration at 50 nM the most potent 10h compound reduced the activity of CDK8 to 35%.

scholarly journals Synthesis and biological evaluation of 2-(4-methylsulfonyl phenyl) indole derivatives: Multi-target compounds with dual antimicrobial and anti-inflammatory activities

2020 ◽  
Author(s):  
Ahmed Shaker ◽  
Eman K. A. Abdelall ◽  
Khaled R. A. Abdellatif ◽  
Hamdy M. Abdel-Rahman
Keyword(s):  
Active Site ◽  
High Selectivity ◽  
Biological Evaluation ◽  
Indole Derivatives ◽  
E Coli ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Synthesis And Biological Evaluation

Abstract Three series of 2-(4-methylsulfonylphenyl) indole derivatives have been designed and synthesized. The synthesized compounds were evaluated for their antimicrobial, COX inhibitory and anti-inflammatory activities. Compound 7g was identified to be the most potent antibacterial candidate against strains of MRSA , E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii , respectively with safe therapeutic dose. Compounds 7a-k, 8a-c and 9a-c showed good anti-inflammatory activity with high selectivity toward COX-2 in comparison with reference drugs indomethacin and celecoxib. Compounds 9a-c were found to release moderate amounts of NO to decrease the side effects associated with selective COX-2 inhibitors. A molecular modeling study for compounds 7b, 7h, and 7i into COX-2 active site correlated with results of in vitro COX-2 inhibition assays.

scholarly journals Synthesis and biological evaluation of 2-(4-methylsulfonyl phenyl)indole derivatives: Multi-target compounds with dual antimicrobial and anti-inflammatory activities

2020 ◽  
Author(s):  
Ahmed M. M. Shaker ◽  
Eman K. A. Abdelall ◽  
Khaled R. A. Abdellatif ◽  
Hamdy M. Abdel-Rahman
Keyword(s):  
Active Site ◽  
High Selectivity ◽  
Biological Evaluation ◽  
Indole Derivatives ◽  
E Coli ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Synthesis And Biological Evaluation

Abstract Three series of 2-(4-methylsulfonylphenyl) indole derivatives have been designed and synthesized. The synthesized compounds were evaluated for their antimicrobial, COX inhibitory and anti-inflammatory activities. Compound 7g was identified to be the most potent antibacterial candidate against strains of MRSA , E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii , respectively with safe therapeutic dose. Compounds 7a-k, 8a-c and 9a-c showed good anti-inflammatory activity with high selectivity toward COX-2 in comparison with reference drugs indomethacin and celecoxib. Compounds 9a-c were found to release moderate amounts of NO to decrease the side effects associated with selective COX-2 inhibitors. A molecular modeling study for compounds 7b, 7h, and 7i into COX-2 active site correlated with results of in vitro COX-2 inhibition assays.

scholarly journals Design, Synthesis, and Biological Evaluation of Pyridazinones Containing the (2-Fluorophenyl) Piperazine Moiety as Selective MAO-B Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5371
Author(s):  
Muhammed Çeçen ◽  
Jong Min Oh ◽  
Zeynep Özdemir ◽  
Saliha Ebru Büyüktuncel ◽  
Mehtap Uysal ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Inhibitory Potency ◽  
Design Synthesis ◽  
Docking Simulations ◽  
Mao B ◽  
Ic50 Value ◽  
Competitive Inhibitors ◽  
Mao A ◽  
Ic50 Values ◽  
Synthesis And Biological Evaluation

Twelve pyridazinones (T1–T12) containing the (2-fluorophenyl) piperazine moiety were designed, synthesized, and evaluated for monoamine oxidase (MAO) -A and -B inhibitory activities. T6 was found to be the most potent MAO-B inhibitor with an IC50 value of 0.013 µM, followed by T3 (IC50 = 0.039 µM). Inhibitory potency for MAO-B was more enhanced by meta bromo substitution (T6) than by para bromo substitution (T7). For para substitution, inhibitory potencies for MAO-B were as follows: -Cl (T3) > -N(CH3)2 (T12) > -OCH3 (T9) > Br (T7) > F (T5) > -CH3 (T11) > -H (T1). T6 and T3 efficiently inhibited MAO-A with IC50 values of 1.57 and 4.19 µM and had the highest selectivity indices (SIs) for MAO-B (120.8 and 107.4, respectively). T3 and T6 were found to be reversible and competitive inhibitors of MAO-B with Ki values of 0.014 and 0.0071, respectively. Moreover, T6 was less toxic to healthy fibroblast cells (L929) than T3. Molecular docking simulations with MAO binding sites returned higher docking scores for T6 and T3 with MAO-B than with MAO-A. These results suggest that T3 and T6 are selective, reversible, and competitive inhibitors of MAO-B and should be considered lead candidates for the treatment of neurodegenerative disorders like Alzheimer’s disease.

Hybrid Design of Isonicotinic Acid Hydrazide Derivatives: Machine Learning Studies, Synthesis and Biological Evaluation of their Antituberculosis Activity

2020 ◽  
Vol 17 (3) ◽  
pp. 365-375
Author(s):  
Vasyl Kovalishyn ◽  
Diana Hodyna ◽  
Vitaliy O. Sinenko ◽  
Volodymyr Blagodatny ◽  
Ivan Semenyuta ◽  
...  
Keyword(s):  
Machine Learning ◽  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Predictive Ability ◽  
Antitubercular Activity ◽  
Biological Evaluation ◽  
Starting Point ◽  
Binary Classifiers ◽  
Synthesis And Biological Evaluation

Background: Tuberculosis (TB) is an infection disease caused by Mycobacterium tuberculosis (Mtb) bacteria. One of the main causes of mortality from TB is the problem of Mtb resistance to known drugs. Objective: The goal of this work is to identify potent small molecule anti-TB agents by machine learning, synthesis and biological evaluation. Methods: The On-line Chemical Database and Modeling Environment (OCHEM) was used to build predictive machine learning models. Seven compounds were synthesized and tested in vitro for their antitubercular activity against H37Rv and resistant Mtb strains. Results: A set of predictive models was built with OCHEM based on a set of previously synthesized isoniazid (INH) derivatives containing a thiazole core and tested against Mtb. The predictive ability of the models was tested by a 5-fold cross-validation, and resulted in balanced accuracies (BA) of 61–78% for the binary classifiers. Test set validation showed that the models could be instrumental in predicting anti- TB activity with a reasonable accuracy (with BA = 67–79 %) within the applicability domain. Seven designed compounds were synthesized and demonstrated activity against both the H37Rv and multidrugresistant (MDR) Mtb strains resistant to rifampicin and isoniazid. According to the acute toxicity evaluation in Daphnia magna neonates, six compounds were classified as moderately toxic (LD50 in the range of 10−100 mg/L) and one as practically harmless (LD50 in the range of 100−1000 mg/L). Conclusion: The newly identified compounds may represent a starting point for further development of therapies against Mtb. The developed models are available online at OCHEM http://ochem.eu/article/11 1066 and can be used to virtually screen for potential compounds with anti-TB activity.

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