Discovery of new nanomolar peroxisome proliferator-activated receptor γ activators via elaborate ligand-based modeling

Al-Najjar, Belal O.; Wahab, Habibah A.; Muhammad, Tengku Sifzizul Tengku; Shu‐Chien, Alexander Chong; Noruddin, Nur Adelina Ahmad; Taha, Mutasem O.

doi:10.1016/j.ejmech.2011.03.040

Cited by 32 publications

(20 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the hydrophobic features were represented by benzyl group, halogen, dimethyl, ethylene as well as the modified alkyl group at terminal nitrogen. As well studied, the classical H 1 -antagonists follows the basic structure consisting of a basic nitrogen atom, predominantly protonated at physiological pH, and two aromatic groups connected via linking group, which can be different chemical natures [22]. Although the indole ring used as the scaffold in this training considered as a non-classical H 1 -antagonists but it presents elements of the general structure.…”

Section: Resultsmentioning

confidence: 99%

Pharmacophore Modeling of N1-alkyltheobromine as Histamine-H1 Receptor Antagonist

Hariono¹,

Wahab²

2015

IJMO

View full text Add to dashboard Cite

Abstract-Previous studies worked on the evaluation a few alkylxanthine derivatives synthesized from theobromine, exhibiting micromolar activities of the compounds against histamine in vitro. The structure-activity relationships study showed that the elongation of alkyl group at N 1 of xanthine ring increased the tracheospasmolytic activity. This result opened the opportunity for alkylxanthine to be developed as antihistamine. Presently, we elucidate the mechanism of N 1 -alkylxanthine derivatives as antihistamine at a molecular level using pharmacophore modeling. The pharmacophore model was generated from a series of Histamine-H1 antagonists employing hydrogen bond acceptor (HBA), hydrogen bond donor (HBD) and two hydrophobic features and used as a search queries to map the N 1 -alkylxanthine derivatives as Histamine-H1 antagonist. The results showed that all the designed ligands can adopt the pharmacophore features model providing the insight understanding about the opportunities of the N 1 -alkylxanthine as Histamine-H1 antagonists.

show abstract

Section: Resultsmentioning

confidence: 99%

Pharmacophore Modeling of N1-alkyltheobromine as Histamine-H1 Receptor Antagonist

Hariono¹,

Wahab²

2015

IJMO

View full text Add to dashboard Cite

show abstract

“…Similarly the reaction of compound 1 with elemental sulphur and ethyl acetoacetate 16 gave the ethyl 5-amino-3-methyl-4-(4-oxo-4,5-dihydrothiazol-2-yl)thiophene-2-carboxylate (17). Compound 17 reacted with either hydrazinehydrate or phenylhydrazine to give the hydrazide derivatives 19a and 19b, respectively (Figure 3).…”

Section: Chemistrymentioning

confidence: 99%

The Synthesis and Cytotoxicity of Novel Thiophene Derivatives Derived from 2-(4-Oxo-4,4-Dihydrothiazol-2-yl) Acetonitrile

Samir¹,

Hamed²

2016

IJOC

View full text Add to dashboard Cite

The reaction of the 2-(4-oxo-4,4-dihydrothiazol-2-yl)acetonitrile 1 with cyaclopentanone (2) afforded the condensed product 3. The latter underwent a series of heterocyclizations through its reaction with different reagents. Moreover, compound 1 underwent the Gewald's thiophene to afford compounds 15 and 17. The reaction of either hydrazine hydrate or phenylhydrazine with compound 17 gave the hydrazide derivatives 19a and 19b, respectively. The cytotoxicity of the newly synthesized products was measured towards the three cancer cell lines MCF-7, NCI-H460 and SF-268. The study showed that compounds 3, 5, 9c, 11, 13a, 13c, 17 and 19b were the most active compounds towards the three cancer cell lines.

show abstract

“…Here, we created a pharmacophore models from a dataset of agonists for PPARreceptor using the Catalyst/Hypogen module for predicting the nutmeg seeds compounds. In the previous study, Najjar et al (2011) generated the pharmacophoric space of PPARg using seven diverse sets of activators (Al-Najjar et al, 2011). However, the compounds screened was not natural compounds.…”

Section: Introductionmentioning

confidence: 99%

The in Silico Study of Nutmeg Seeds (Myristica fragrans Houtt) as Peroxisome Proliferator Activated Receptor Gamma Activator Using 3D-QSAR Pharmacophore Modelling

Muchtaridi¹,

Low²,

Lestari³

2016

J App Pharm Sci

View full text Add to dashboard Cite

In this study, we created a pharmacophore models from a dataset of agonists for PPAR gamma receptor using the Catalyst/Hypogen module. A training set consists of 22 compounds activity range between 0.1 to 3,500 nM, were carefully selected. In previous study, molecular docking of macelignan against PPARγ binding pocket showed a free energy binding of -11.07 kJ/mol, interaction with the hydrophobic pocket (diphenyl pocket) (Celik et al., 2007), and a hydrogen bond network (His323, Tyr473, His449 and Ser289). The pharmacophore model (Hypo1), consisting of 5 features, i.e. one hydrogen bond acceptor (HBA), negative ionizable (NI), ring aromatic (RA) and two hydrophobics (HY) features, and one excluded volume. Hypo1 has the lowest total cost value (92.055), the highest cost difference (40.9316), the lowest RMSD (0.591049), and the best correlation coefficient (0.972949). Fourteen natural substances reported from nutmeg seeds (Myristica fragrans HOUTT.) were then mapped against Hypo1, and macelignan shows a fair fit value of 7.00102 with an estimated value of 1271.990 nM. This concludes, macelignant in nutmeg might have antidiabetic properties via PPARγ receptor activation.

show abstract

Discovery of new nanomolar peroxisome proliferator-activated receptor γ activators via elaborate ligand-based modeling

Cited by 32 publications

References 81 publications

Pharmacophore Modeling of N1-alkyltheobromine as Histamine-H1 Receptor Antagonist

Pharmacophore Modeling of N1-alkyltheobromine as Histamine-H1 Receptor Antagonist

The Synthesis and Cytotoxicity of Novel Thiophene Derivatives Derived from 2-(4-Oxo-4,4-Dihydrothiazol-2-yl) Acetonitrile

The in Silico Study of Nutmeg Seeds (Myristica fragrans Houtt) as Peroxisome Proliferator Activated Receptor Gamma Activator Using 3D-QSAR Pharmacophore Modelling

Contact Info

Product

Resources

About