Synthesis, biological evaluation, and molecular docking of new series of antitumor and apoptosis inducers designed as VEGFR-2 inhibitors

A class of 1-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol derivatives (4a-t) has been synthesized in good yields through a three component coupling reaction. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against five cell lines such as DU145 (human prostate cancer), MDA-MB-B231 (human breast cancer), SKOV3 (human ovarian cancer), B16-F10 (mouse skin melanoma) and CHO-K1 (Chinese hamster ovary cells), a noncancerous cell line. In vitro inhibitory activity indicates that compounds 4a, 4b, 4c, 4d, 4g, 4j, and 4o exhibited potent anti-proliferative behavior. Among them, compounds 4g, 4j and 4o found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking facilitates to investigate the probable binding mode and key active site interactions in tubulins α and β proteins. The docking results are complementary to experimental results.

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Synthesis, Molecular Docking Studies and Biological Evaluation o f 3-Iminoaurones as Acetylcholinesterase and Butyrylcholinesterase Inhibitors

Letters in Drug Design & Discovery ◽

10.2174/1570180814666170106123959 ◽

2017 ◽

Vol 14 (9) ◽

Cited By ~ 3

Author(s):

Ehsan Ullah Mughal ◽

Amina Sadiq ◽

Bilal Ahmad Khan ◽

Muhammad Naveed Zafar ◽

Ishtiaq Ahmed ◽

...

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

Biological Evaluation ◽

Molecular Docking Studies

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Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Trimethoxy-ring Derivatives as BRD4 Inhibitors

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180322115056 ◽

2018 ◽

Vol 15 ◽

Author(s):

Yan Yang ◽

Zhiyi Yao

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

Biological Evaluation ◽

Molecular Docking Studies

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Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

Medicinal Chemistry ◽

10.2174/1573406415666190724142951 ◽

2020 ◽

Vol 16 (7) ◽

pp. 892-902 ◽

Cited By ~ 3

Author(s):

Aida Iraji ◽

Mahsima Khoshneviszadeh ◽

Pegah Bakhshizadeh ◽

Najmeh Edraki ◽

Mehdi Khoshneviszadeh

Keyword(s):

Molecular Docking ◽

Active Site ◽

Competitive Inhibition ◽

Docking Study ◽

Biological Evaluation ◽

Primary Response ◽

Ratio Method ◽

Molecular Docking Study ◽

Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

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Facile Synthesis and Biological Evaluation of New Mannich Products as Potential Antibacterial, Antifungal and Antituberculosis Agents: Molecular Docking Study

Current Bioactive Compounds ◽

10.2174/1573407212666160517145130 ◽

2016 ◽

Vol 13 (1) ◽

pp. 47-58 ◽

Cited By ~ 17

Author(s):

Hitendra M. Patel ◽

Kinjal D. Patel ◽

Hitesh D. Patel

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Biological Evaluation ◽

Facile Synthesis ◽

Molecular Docking Study ◽

Synthesis And Biological Evaluation

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Synthesis and Biological Evaluation of a Novel Glycidyl Metharcylate/Phaytic Acid-Based on Bagasse Xylan Composite Derivative

Polymers ◽

10.3390/polym13132084 ◽

2021 ◽

Vol 13 (13) ◽

pp. 2084

Author(s):

Mingkun Li ◽

Heping Li ◽

Hongli Liu ◽

Zhiming Zou ◽

Chaoyu Xie

Keyword(s):

Lung Cancer ◽

Thermal Stability ◽

Ionic Liquid ◽

Molecular Docking ◽

Phytic Acid ◽

Biological Activities ◽

Biological Evaluation ◽

Potential Candidate ◽

Reaction Conditions ◽

Cell Proliferation Inhibition

The development of natural biomass materials with excellent properties is an attractive way to improve the application range of natural polysaccharides. Bagasse Xylan (BX) is a natural polysaccharide with various biological activities, such as antitumor, antioxidant, etc. Its physic-chemical and biological properties can be improved by functionalization. For this purpose, a novel glycidyl metharcylate/phytic acid based on a BX composite derivative was synthesized by a free radical polymerization technique with glycidyl metharcylate (GMA; GMABX) and further esterification with phytic acid (PA; GMABX-PA) in ionic liquid. The effects of the reaction conditions (i.e., temperature, time, initiator concentration, catalyst concentration, GMA concentration, PA concentration, mass of ionic liquid) on grafting rate(G), conversion rate(C) and degree of substitution(DS) are discussed. The structure of the composite material structure was confirmed by FTIR, 1H NMR and XRD. SEM confirmed the particle morphology of the composite derivative. The thermal stability of GMABX-PA was determined by TG-DTG. Molecular docking was further performed to study the combination mode of the GMABX-PA into the active site of two lung cancer proteins (5XNV, 2EB2) and a blood cancer protein (2M6N). In addition, tumor cell proliferation inhibition assays for BX, GMABX-PA were carried out using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetraz -olium bromide (MTT) method. The results showed that various reaction conditions exhibited favorable gradient curves, and that a maximum G of 56% for the graft copolymerization and a maximum DS of 0.267 can be achieved. The thermal stability was significantly improved, as demonstrated by the fact that there was still 60% residual at 800 °C. The molecular docking software generated satisfactory results with regard to the evaluated binding energy and combining sites. The inhibition ratio of GMABX-PA on NCI-H460 (lung cancer cells) reached 29.68% ± 4.45%, which is five times higher than that of BX. Therefore, the material was shown to be a potential candidate for biomedical applications as well as for use as a heat resistant material.

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