Rational Design, Synthesis, Biological Evaluation, Homology and Docking Studies of Coumarin Derivatives as α1-Adrenoceptor Antagonists

2011 ◽  
Vol 8 (6) ◽  
pp. 1052-1064 ◽  
Author(s):  
Xiang Zhou ◽  
Ya-Dong Chen ◽  
Tao Wang ◽  
Xiao-Bing Wang ◽  
Ling-Yi Kong
Keyword(s):  
Rational Design ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Coumarin Derivatives ◽  
Design Synthesis

scholarly journals Novel 1-Amidino-4-Phenylpiperazines as Potent Agonists at Human TAAR1 Receptor: Rational Design, Synthesis, Biological Evaluation and Molecular Docking Studies

2020 ◽  
Vol 13 (11) ◽  
pp. 391 ◽  
Author(s):  
Valeria Francesconi ◽  
Elena Cichero ◽  
Evgeny V. Kanov ◽  
Erik Laurini ◽  
Sabrina Pricl ◽  
...  
Keyword(s):  
Rational Design ◽  
Pharmacophore Model ◽  
Docking Studies ◽  
Biological Evaluation ◽  
The Novel ◽  
Design Synthesis ◽  
Innovative Therapies ◽  
Spatial Geometry ◽  
Targeting Ability ◽  
20 Nm

Targeting trace amine-associated receptor 1 (TAAR1) receptor continues to offer an intriguing opportunity to develop innovative therapies in different pharmacological settings. Pursuing our endeavors in the search for effective and safe human TAAR1 (hTAAR1) ligands, we synthesized a new series of 1-amidino-4-phenylpiperazine derivatives (1–16) based on the application of a combined pharmacophore model/scaffold simplification strategy for an in-house series of biguanide-based TAAR1 agonists. Most of the novel compounds proved to be more effective than their prototypes, showing nanomolar EC50 values in functional activity at hTAAR1 and low general cytotoxicity (CC50 > 80 µM) when tested on the Vero-76 cell line. In this new series, the main determinant for TAAR1 agonism ability appears to result from the appropriate combination between the steric size and position of the substituents on the phenyl ring rather than from their different electronic nature, since both electron-withdrawing and electron donor groups are permitted. In particular, the ortho-substitution seems to impose a more appropriate spatial geometry to the molecule that entails an enhanced TAAR1 potency profile, as experienced, in the following order, by compounds 15 (2,3-diCl, EC50 = 20 nM), 2 (2-CH3, EC50 = 30 nM), 6 (2-OCH3, EC50 = 93 nM) and 3 (2-Cl, EC50 = 160 nM). Apart from the interest in them as valuable leads for the development of promising hTAAR1 agonists, these simple small molecules have further allowed us to identify the minimal structural requirements for producing an efficient hTAAR1 targeting ability.

scholarly journals Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4718
Author(s):  
Lamya H. Al-Wahaibi ◽  
Bahaa G. M. Youssif ◽  
Ehab S. Taher ◽  
Ahmed H. Abdelazeem ◽  
Antar A. Abdelhamid ◽  
...  
Keyword(s):  
Proliferative Activity ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Selectivity Ratio ◽  
Computational Studies ◽  
Design Synthesis ◽  
Ca Ix ◽  
Side Pocket ◽  
Modelling Simulation ◽  
Good Agreement

A novel series of tri-aryl imidazole derivatives 5a–n carrying benzene sulfonamide moiety has been designed for their selective inhibitory against hCA IX and XII activity. Six compounds were found to be potent and selective CA IX inhibitors with the order of 5g > 5b > 5d > 5e > 5g > 5n (Ki = 0.3–1.3 μM, and selectivity ratio for hCA IX over hCA XII = 5–12) relative to acetazolamide (Ki = 0.03 μM, and selectivity ratio for hCA IX over hCA XII = 0.20). The previous sixth inhibitors have been further investigated for their anti-proliferative activity against four different cancer cell lines using MTT assay. Compounds 5g and 5b demonstrated higher antiproliferative activity than other tested compounds (with GI50 = 2.3 and 2.8 M, respectively) in comparison to doxorubicin (GI50 = 1.1 M). Docking studies of these two compounds adopted orientation and binding interactions with a higher liability to enter the active side pocket CA-IX selectively similar to that of ligand 9FK. Molecular modelling simulation showed good agreement with the acquired biological evaluation.

scholarly journals N,N′-Disubstituted thiourea and urea derivatives: design, synthesis, docking studies and biological evaluation against nitric oxide synthase

MedChemComm ◽  
2016 ◽  
Vol 7 (4) ◽  
pp. 667-678 ◽  
Author(s):  
Mariem Chayah ◽  
M. Encarnación Camacho ◽  
M. Dora Carrión ◽  
Miguel A. Gallo ◽  
Miguel Romero ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Urea Derivatives ◽  
Design Synthesis ◽  
Inos Inhibitors ◽  
Oxide Synthase

N,N′-Disubstituted thioureas and ureas as nNOS and iNOS inhibitors were synthesized. Thiourea 4g was the best inhibitor without eNOS inhibition.

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