scholarly journals Synthesis and docking studies of renin inhibitors containing ester and amide derivatives of (3S, 4S)-4-amino-hydroxy acids with S3-S3’ renin binding site.

2021 ◽  
Vol 78 (1) ◽  
pp. 55-70
Author(s):  
Iwona Winiecka ◽  
Dorota Marszałek ◽  
Paweł Jaworski ◽  
Andrzej Mazurek ◽  
Artur Wierzbowski ◽  
...  
MedChemComm ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 961-969 ◽  
Author(s):  
Godwin Akpeko Dziwornu ◽  
Stephanie Kamunya ◽  
Tando Ntsabo ◽  
Kelly Chibale

Fusidic acid is a natural product antibiotic used clinically, primarily against staphylococcal infections.


2019 ◽  
Vol 19 (13) ◽  
pp. 1093-1110 ◽  
Author(s):  
Adel A.H. Abdel Rahman ◽  
Ibrahim F. Nassar ◽  
Amira K.F. Shaban ◽  
Dina S. EL-Kady ◽  
Hanem M. Awad ◽  
...  

Background & Objective:New diaryl-substituted pyrimidinedione compounds, their thioxo derivatives as well as their bicyclic thiazole compounds were synthesized and characterized.Methods:The glycosylamino derivatives of the synthesized disubstituted derivatives of the pyrimidine scaffold were also prepared via reaction of the N3-amino derivatives with a number of monosaccharides followed by acetylation.Results:The anticancer activity of the synthesized compounds was studied against human liver cancer (HepG2) and RPE-1cell lines. Compounds 2a, 2b, 3a and 12 showed potent activities with IC50 results comparable to that of doxorubicin.Conclusion:Docking investigations into Cyclin-dependent kinase 2 (CDK-2) enzyme, a potential target for cancer medication, were also reported showing the possible binding interaction into the enzyme active site to support their activity behavior.


Author(s):  
Shikha Sharma ◽  
Shweta Sharma ◽  
Vaishali Pathak ◽  
Parwinder Kaur ◽  
Rajesh Kumar Singh

Aim: To investigate and validate the potential target proteins for drug repurposing of newly FDA approved antibacterial drug. Background: Drug repurposing is the process of assigning indications for drugs other than the one(s) that they were initially developed for. Discovery of entirely new indications from already approved drugs is highly lucrative as it minimizes the pipeline of the drug development process by reducing time and cost. In silico driven technologies made it possible to analyze molecules for different target proteins which are not yet explored. Objective: To analyze possible targets proteins for drug repurposing of lefamulin and their validation. Also, in silico prediction of novel scaffolds from lefamulin has been performed for assisting medicinal chemists in future drug design. Methods: A similarity-based prediction tool was employed for predicting target protein and further investigated using docking studies on PDB ID: 2V16. Besides, various in silico tools were employed for prediction of novel scaffolds from lefamulin using scaffold hopping technique followed by evaluation with various in silico parameters viz., ADME, synthetic accessibility and PAINS. Results: Based on the similarity and target prediction studies, renin is found as the most probable target protein for lefamulin. Further, validation studies using docking of lefamulin revealed the significant interactions of lefamulin with the binding pocket of the target protein. Also, three novel scaffolds were predicted using scaffold hopping technique and found to be in the limit to reduce the chances of drug failure in the physiological system during the last stage approval process. Conclusion: To encapsulate the future perspective, lefamulin may assist in the development of the renin inhibitors and, also three possible novel scaffolds with good pharmacokinetic profile can be developed into both as renin inhibitors and for bacterial infections.


2013 ◽  
Vol 9 (7) ◽  
pp. 920-925 ◽  
Author(s):  
Yi Bi ◽  
Jinyi Xu ◽  
Fei Sun ◽  
Xiaoming Wu ◽  
Wencai Ye ◽  
...  

Author(s):  
Vasil Tsanov ◽  
Hristo Tsanov

Background:: This article concentrates on the processes occurring in the medium around the cancer cell and the transfer of glycoside amides through their cell membrane. They are obtained by modification of natural glycoside-nitriles (cyano-glycosides). Hydrolysis of starting materials in the blood medium and associated volume around physiologically active healthy and cancer cells, based on quantum-chemical semi-empirical methods, is considered. Objective:: Based on the fact that the cancer cell feeds primarily on carbohydrates, it is likely that organisms have adapted to take food containing nitrile glycosides and / or modified forms to counteract "external" bioactive activity. Cancers, for their part, have evolved to create conditions around their cells that eliminate their active apoptotic forms. This is far more appropriate for them than changing their entire enzyme regulation to counteract it. In this way, it protects itself and the gene sets and develops according to its instructions. Methods:: Derived pedestal that closely defines the processes of hydrolysis in the blood, the transfer of a specific molecular hydrolytic form to the cancer cell membrane and with the help of time-dependent density-functional quantum- chemical methods, its passage and the processes of re-hydrolysis within the cell itself, to forms causing chemical apoptosis of the cell - independent of its non-genetic set, which seeks to counteract the process. Results:: Used in oncology it could turn a cancer from a lethal to a chronic disease (such as diabetes). The causative agent and conditions for the development of the disease are not eliminated, but the amount of cancer cells could be kept low for a long time (even a lifetime). Conclusion:: The amide derivatives of nitrile glycosides exhibit anti-cancer activity, the cancer cell probably seeks to displace hydrolysis of these derivatives in a direction that would not pass through its cell membrane and the amide- carboxyl derivatives of nitrile glycosides could deliver extremely toxic compounds within the cancer cell itself and thus block and / or permanently damage its normal physiology.


ACS Omega ◽  
2021 ◽  
Author(s):  
Qiang Shang ◽  
Xiaobo Zhou ◽  
Ming-Rong Yang ◽  
Jing-Guang Lu ◽  
Yu Pan ◽  
...  

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