Integrating regression and classification-based QSARs with molecular docking analyses to explore the structure-antiaromatase activity relationships of letrozole-based analogs

2017 ◽  
Vol 95 (12) ◽  
pp. 1285-1295 ◽  
Author(s):  
Nilanjan Adhikari ◽  
Sk. Abdul Amin ◽  
Tarun Jha ◽  
Shovanlal Gayen
Keyword(s):  
Cyano Group ◽  
Triazole Ring ◽  
Imidazole Ring ◽  
Structural Features ◽  
Ring System ◽  
Heme Iron ◽  
Enzyme Active Site ◽  
Hydrogen Bonding Interactions ◽  
Azole Ring ◽  
Better Than

Aromatase is a multienzyme complex responsible for the biosynthesis of estrogen and its level has been found higher in breast cancer. Although the designing strategy of aromatase inhibitors (AIs) has continued for more than four decades, it may still be in demand to design highly effective and less toxic AIs. In this study, several chemometric approaches have been used to explore the important structural features of a series of letrozole-based analogs for their promising aromatase inhibitory activity. All techniques are statistically validated individually and in turn, validated with each other along with the structure–activity relationship (SAR) observations. The imidazole ring has been found to interact with the heme iron, whereas the triazole ring system has not shown any interaction. Moreover, imidazole function is better than 1,2,3-triazole, whereas 1,2,3-triazole is better than the 1,2,5-triazole ring system. Additionally, a bulky aryl substitution in the azole ring along with the orientation of the azole nitrogens and the cyanophenyl function has an essential role in the inhibition of aromatase. Furthermore, a cyano group substituted at the phenyl moiety interacts with Arg115, Met374, and Ser478 at the enzyme active site to form hydrogen bonding interactions. These observations are useful for designing potential AIs in the future.

Novel molecules containing structural features of NSAIDs and 1,2,3-triazole ring: design, synthesis and evaluation as potential cytotoxic agents

2021 ◽  
pp. 131222
Author(s):  
Jyoti Mareddy ◽  
Kazi Amirul Hossain ◽  
N. Sudhakar Yadav ◽  
Venkanna Banothu ◽  
Jaya Shree Anireddy ◽  
...  
Keyword(s):  
Triazole Ring ◽  
Structural Features ◽  
Cytotoxic Agents ◽  
Design Synthesis

Efficient Synthesis of Novel N-[4-Methyl-3-(4-(5-phenyl-1,3,4-oxadiazol-2-yl)phenyl)thiazol-2(3H)-ylidene]benzamide Hybrid Ring System as Potential Antibacterial Agents

2021 ◽  
Vol 17 ◽  
Author(s):  
Hummera Rafique ◽  
Aamer Saeed ◽  
Muhammad Naseem ◽  
Tauqeer Riaz ◽  
Fouzia Perveen ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Antioxidant Activities ◽  
Antibacterial Properties ◽  
Antibacterial Activities ◽  
Structural Features ◽  
Ring System ◽  
Biologically Active ◽  
Thiazole Ring ◽  
Spectroscopic Techniques ◽  
Hybrid Ring

Background: Heterocyclic compounds display versatile biological applications, so the aim of this paper was to prepare biologically important heterocycles with enhanced bacterial resistance and to evaluate for their various structural features that are responsible for their biological properties. Objective: The objective was to synthesize bacterial resistance compounds with enhanced antibacterial properties. Method: Ester moiety containing thiazole ring was converted into its hydrazide derivatives. These heterocyclic derivatives were cyclized into another ring oxadiazole; hence a hybrid ring system of two biologically active rings was prepared. Result: All the synthesized compounds were characterized by spectroscopic techniques and were screened for their antibacterial potential; they possess significant antibacterial activities. Conclusion: New hybrid heterocyclic ring systems were synthesized by cyclization of hydrazide derivatives by adopting two step strategy in good yields. All the synthesized compounds were evaluated for their antioxidant activities; they showed moderate to significant activities. QSAR and Molecular docking studies were performed to determine the mode of interaction. Experimental and computational data is in accordance with the determined antibacterial activities.

scholarly journals 6-Methyl-4-{[4-(trimethylsilyl)-1H-1,2,3-triazol-1-yl]methyl}-2H-chromen-2-one

IUCrData ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Sowmiya Carmel Y. ◽  
N. L. Prasad ◽  
Noor Shahina Begum ◽  
Hari Prasad Suresh
Keyword(s):  
Dihedral Angle ◽  
Title Compound ◽  
Triazole Ring ◽  
Ring System ◽  
Compound C ◽  
Coumarin Ring

In the title compound, C16H19N3O2Si, the dihedral angle between the coumarin ring system (r.m.s. deviation = 0.031 Å) and the triazole ring is 73.81 (8)°. In the crystal, molecules are linked into [010] chains by weak C—H...O interactions.

Design and Synthesis of Novel Sulfonamide-Derived Triazoles and Bioactivity Exploration

2020 ◽  
Vol 16 (1) ◽  
pp. 104-118 ◽  
Author(s):  
Shi-Chao He ◽  
Hui-Zhen Zhang ◽  
Hai-Juan Zhang ◽  
Qing Sun ◽  
Cheng-He Zhou
Keyword(s):  
Chlorosulfonic Acid ◽  
Antibacterial Activities ◽  
Structural Features ◽  
The Novel ◽  
E Coli ◽  
Design And Synthesis ◽  
Chemical Studies ◽  
Antimicrobial Evaluation ◽  
Better Than

Objective: Due to the incidence of resistance, a series of sulfonamide-derived 1,2,4- triazoles were synthesized and evaluated. Method: The novel sulfonamide-derived 1,2,4-triazoles were prepared starting from commercial acetaniline and chlorosulfonic acid by sulfonylation, aminolysis, N-alkylation and so on. The antimicrobial activity of the synthesized compounds were evaluated in vitro by two-fold serial dilution technique. Results: In vitro antimicrobial evaluation found that 2-chlorobenzyl sulfonamide 1,2,4-triazole 7c exhibited excellent antibacterial activities against MRSA, B. subtilis, B. typhi and E. coli with MIC values of 0.02−0.16 μmol/mL, which were comparable or even better than Chloromycin. The preliminary mechanism suggested that compound 7c could effectively bind with DNA, and also it could bind with human microsomal heme through hydrogen bonds in molecular docking. Computational chemical studies were performed on compound 7c to understand the structural features that are essential for activity. Additionally, compound 7c could generate a small amount of reactive oxygen species (ROS). Conclusion: Compound 7c could serve as a potential clinical antimicrobial candidate.

scholarly journals rac-N-Benzylisatincreatinine (unknown solvate)

2013 ◽  
Vol 69 (2) ◽  
pp. o290-o291
Author(s):  
Narsimha Reddy Penthala ◽  
Peter A. Crooks
Keyword(s):  
Acetic Acid ◽  
Hydrogen Bonds ◽  
Sodium Acetate ◽  
Aldol Condensation ◽  
Mixed Solvents ◽  
Imidazole Ring ◽  
Ring System ◽  
Dihedral Angles ◽  
Acta Cryst ◽  
Compound C

The title compound, C19H18N4O3[systematic name: (RS)-1-benzyl-3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)-2,3-dihydro-1H-indol-2-one], was prepared as a racemate (RRandSS) by the aldol condensation ofN-benzylisatin with creatinine in the presence of sodium acetate in acetic acid. The r.m.s. deviation of the isatin ring system is 0.033 Å. The benzyl group is disordered over two orientations, with refined occupancies of 0.847 (7) and 0.153 (7). The dihedral angles between the isatin ring system and the benzene ring (major disorder component) and the imidazole ring are 82.82 (7) and 51.31 (3)°, respectively, In the crystal, molecules are linked into (001) sheets by N—H...O and O—H...N hydrogen bonds, which incorporateR22(9) ring motifs. The crystal was grown from mixed solvents (ethanol, methanol and possibly also ethyl acetate). These solvents are disordered in the crystal and the resulting electron density was found to be uninterpretable. The solvent contribution to the scattering was removed with the SQUEEZE routine inPLATON[Spek (2009).Acta Cryst.D65, 148–155]. The formula mass and density do not take account of the solvent.

Synthesis of Novel Isoindolo[2,1-a]quinazolinedione Derivatives Containing a 1,2,3-Triazole Ring System

2016 ◽  
Vol 99 (1) ◽  
pp. 37-40 ◽  
Author(s):  
Fatemeh Esmaeili-Marandi ◽  
Mina Saeedi ◽  
Issa Yavari ◽  
Mohammad Mahdavi ◽  
Abbas Shafiee
Keyword(s):  
Triazole Ring ◽  
Ring System

scholarly journals SEM morphological analysis of irradiated polystyrene film doped by a Schiff base containing a 1,2,4-triazole ring system

2019 ◽  
Vol 9 (3-4) ◽  
pp. 169-177 ◽  
Author(s):  
Ahmed A. Ahmed ◽  
Dina S. Ahmed ◽  
Gamal A. El-Hiti ◽  
Mohammad Hayal Alotaibi ◽  
Hassan Hashim ◽  
...  
Keyword(s):  
Schiff Base ◽  
Surface Morphology ◽  
Ultraviolet Light ◽  
Fibrous Material ◽  
Morphological Analysis ◽  
Irradiation Time ◽  
Triazole Ring ◽  
Ring System ◽  
Polystyrene Film ◽  
Low Concentration

Abstract A Schiff base containing the 1,2,4-triazole moiety was synthesized and added to polystyrene at low concentration for a homogenous blend. The polystyrene film was irradiated with ultraviolet light and the surface morphology was analyzed. Micrographs of the polystyrene/Schiff base blend after irradiation indicated the fabrication of a terrestrial crack-like material. This was ascribed to the presence of the Schiff base, relatively long irradiation time, and photostability induced by the base. After irradiation, the blank polystyrene film formed a cotton-like fibrous material.

Synthesis of Novel Benzimidazole and Benzothiazole Derivatives Bearing a 1,2,3-triazole Ring System and their Acetylcholinesterase Inhibitory Activity

2017 ◽  
Vol 41 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Laleh Faraji ◽  
Shiva Shahkarami ◽  
Hamid Nadri ◽  
Alireza Moradi ◽  
Mina Saeedi ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Docking Simulation ◽  
Triazole Ring ◽  
Copper Catalysts ◽  
Inhibitory Effect ◽  
Ring System ◽  
Benzothiazole Derivatives ◽  
Ache Inhibitory Activity ◽  
Group A

A series of 20 novel benzimidazole and benzothiazole derivatives linked to a 1,2,3-triazole ring system was synthesised, characterised and evaluated for in vitro acetylcholinesterase (AChE) inhibitory activity. Several copper catalysts and solvents were screened to establish the optimal conditions for the preparation of the target compounds. Three different linkers were used to optimise the enzyme inhibitory effect. Out of the 20 compounds, 13 showed some AChE inhibition. The most potent compound, which showed 84% inhibition at 100 μM, contained a 1-(2-fluorobenzyl)-1,2,3-triazole linked to a benzimidazole group. A docking simulation study showed that the most active compound bound preferentially to the catalytic anionic subsite of the AChE enzyme.

A Series of Imidazolyl-Containing Bisphosphonates with Abundant Hydrogen-Bonding Interactions: Syntheses, Structures, and Bone-Binding Affinity

2014 ◽  
Vol 67 (2) ◽  
pp. 192 ◽  
Author(s):  
Ling Qiu ◽  
Jianguo Lin ◽  
Liqing Wang ◽  
Wen Cheng ◽  
Yang Cao ◽  
...  
Keyword(s):  
High Performance ◽  
Binding Capacity ◽  
Imidazole Ring ◽  
Binding Affinities ◽  
Robust Method ◽  
X Ray Diffraction ◽  
X Ray ◽  
Hydrogen Bonding Interactions ◽  
Alkyl Groups ◽  
Hydroxy Groups

A series of novel bisphosphonates (BPs) were designed and synthesised as longer-chain analogues of the clinically widely used BP–zoledronate (ZL). They were characterised by mass spectrometry, infrared spectroscopy, NMR spectroscopy, and single-crystal X-ray diffraction. All the crystals are zwitterions with one of the phosphonate oxygen atoms deprotonated and the hydrogen atom transferred to the nitrogen of the imidazole ring. A lot of strong hydrogen bonds are observed among the phosphonate oxygens, hydroxy groups, and protonated nitrogen atoms. An accurate, precise, and robust method was developed to determine the bone binding affinities of BPs based on high performance liquid chromatography. The results show that these five BPs have a strong affinity for hydroxyapatite and the binding capacity decreases when the substituted alkyl groups increase in size.

scholarly journals In Silico Screening of Semi-Synthesized Compounds as Potential Inhibitors for SARS-CoV-2 Papain-Like Protease: Pharmacophoric Features, Molecular Docking, ADMET, Toxicity and DFT Studies

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6593
Author(s):  
Mohamed S. Alesawy ◽  
Eslam B. Elkaeed ◽  
Aisha A. Alsfouk ◽  
Ahmed M. Metwaly ◽  
Ibrahim. H. Eissa
Keyword(s):  
Structural Features ◽  
Docking Studies ◽  
Proteolytic Processing ◽  
Binding Modes ◽  
Free Energies ◽  
Essential Enzyme ◽  
Potential Inhibitors ◽  
Molecular Electrostatic Potential Maps ◽  
Better Than ◽  
Binding Free Energies

Papain-like protease is an essential enzyme in the proteolytic processing required for the replication of SARS-CoV-2. Accordingly, such an enzyme is an important target for the development of anti-SARS-CoV-2 agents which may reduce the mortality associated with outbreaks of SARS-CoV-2. A set of 69 semi-synthesized molecules that exhibited the structural features of SARS-CoV-2 papain-like protease inhibitors (PLPI) were docked against the coronavirus papain-like protease (PLpro) enzyme (PDB ID: (4OW0). Docking studies showed that derivatives 34 and 58 were better than the co-crystallized ligand while derivatives 17, 28, 31, 40, 41, 43, 47, 54, and 65 exhibited good binding modes and binding free energies. The pharmacokinetic profiling study was conducted according to the four principles of the Lipinski rules and excluded derivative 31. Furthermore, ADMET and toxicity studies showed that derivatives 28, 34, and 47 have the potential to be drugs and have been demonstrated as safe when assessed via seven toxicity models. Finally, comparing the molecular orbital energies and the molecular electrostatic potential maps of 28, 34, and 47 against the co-crystallized ligand in a DFT study indicated that 28 is the most promising candidate to interact with the target receptor (PLpro).

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