Lavendamycin Antitumor Agents: Structure-Based Design, Synthesis, and NAD(P)H:Quinone Oxidoreductase 1 (NQO1) Model Validation with Molecular Docking and Biological Studies

2008 ◽  
Vol 51 (11) ◽  
pp. 3104-3115 ◽  
Author(s):  
Mary Hassani ◽  
Wen Cai ◽  
Katherine H. Koelsch ◽  
David C. Holley ◽  
Anthony S. Rose ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Model Validation ◽  
Antitumor Agents ◽  
Design Synthesis ◽  
Biological Studies

scholarly journals Design, Synthesis and Comprehensive Investigations of Pyrrolo[3,4-d]pyridazinone-Based 1,3,4-Oxadiazole as New Class of Selective COX-2 Inhibitors

2020 ◽  
Vol 21 (24) ◽  
pp. 9623
Author(s):  
Łukasz Szczukowski ◽  
Edward Krzyżak ◽  
Adrianna Zborowska ◽  
Patrycja Zając ◽  
Katarzyna Potyrak ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
One Pot ◽  
Design Synthesis ◽  
Biological Studies ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Dna Strand ◽  
Cox 2 Inhibitors

The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in treatment of different chronic inflammatory disorders is strongly restricted by their serious gastrointestinal adverse effects. Therefore, there is still an urgent need to search for new, safe, and efficient anti-inflammatory agents. Previously, we have reported the Mannich base-type derivatives of pyrrolo[3,4-d]pyridazinone which strongly inhibit cyclooxygenase, have better affinity to COX-2 isoenzyme and exert promising anti-oxidant activity. These findings encouraged us to perform further optimization of that structure. Herein, we present the design, synthesis, molecular docking, spectroscopic, and biological studies of novel pyrrolo[3,4-d]pyridazinone derivatives bearing 4-aryl-1-(1-oxoethyl)piperazine pharmacophore 5a,b–6a,b. The new compounds were obtained via convenient, efficient, one-pot synthesis. According to in vitro evaluations, novel molecules exert no cytotoxicity and act as selective COX-2 inhibitors. These findings stay in good correlation with molecular modeling results, which additionally showed that investigated compounds take a position in the active site of COX-2 very similar to Meloxicam. Moreover, all derivatives reduce the increased level of reactive oxygen and nitrogen species and prevent DNA strand breaks caused by oxidative stress. Finally, performed spectroscopic and molecular docking studies demonstrated that new compound interactions with bovine serum albumin (BSA) are moderate, formation of complexes is in one-to-one ratio, and binding site II (subdomain IIIA) is favorable.

scholarly journals Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1209 ◽  
Author(s):  
Liwei Ma ◽  
Haijun Wang ◽  
Jing Wang ◽  
Lei Liu ◽  
Song Zhang ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Antitumor Agents ◽  
Human Cancer ◽  
Side Chain ◽  
Design Synthesis ◽  
Apoptosis Pathway ◽  
Human Cancer Cell Lines ◽  
Biological Studies ◽  
Intrinsic Apoptosis Pathway

A series of novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone (7a–g) or thiosemicarbazone (7h–k) side chain were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, HCT-116, MCF-7, and A549) using the MTT assay in vitro. The results showed that compound 7j exhibited significant cytotoxic activity against HepG2 cells (IC50 = 3.52 μM), being more potent than ergosterol peroxide. Further cellular mechanism studies in HepG2 cells indicated that compound 7j triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential (MMP), which was associated with up-regulation of Bax, down-regulation of Bcl-2, activation levels of the caspase cascade, and formation of reactive oxygen species (ROS). The above findings indicated that compound 7j may be used as a promising skeleton for antitumor agents with improved efficacy.

Design, synthesis, biological evaluation and molecular docking of new 1,3,4-oxadiazole homonucleosides and their double-headed analogs as antitumor agents

2020 ◽  
pp. 104558
Author(s):  
Az-eddine EL Mansouri ◽  
Ali Oubella ◽  
Ahmad Mehdi ◽  
Moulay Youssef AitItto ◽  
Mohamed Zahouily ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antitumor Agents ◽  
Biological Evaluation ◽  
Design Synthesis

scholarly journals Design, synthesis, molecular docking, and biological studies of novel phytoestrogen-tanaproget hybrids

2016 ◽  
Vol 46 (5) ◽  
pp. 460-474 ◽  
Author(s):  
Sumit Kumar ◽  
Nishant Verma ◽  
Nikhil Kumar ◽  
Alok Patel ◽  
Partha Roy ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Design Synthesis ◽  
Biological Studies

Design, synthesis and molecular docking of novel structural hybrids of substituted isatin based pyrazoline and thiadiazoline as antitumor agents

2017 ◽  
Vol 26 (4) ◽  
pp. 819-829 ◽  
Author(s):  
Kiran Gangarapu ◽  
Gouthami Thumma ◽  
Sarangapani Manda ◽  
Anvesh Jallapally ◽  
Ravi Jarapula ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antitumor Agents ◽  
Design Synthesis

scholarly journals Antitumor Agents 288: Design, Synthesis, SAR, and Biological Studies of Novel Heteroatom-Incorporated Antofine and Cryptopleurine Analogues as Potent and Selective Antitumor Agents

2011 ◽  
Vol 54 (14) ◽  
pp. 5097-5107 ◽  
Author(s):  
Xiaoming Yang ◽  
Qian Shi ◽  
Shuenn-Chen Yang ◽  
Chi-Yuan Chen ◽  
Sung-Liang Yu ◽  
...  
Keyword(s):  
Antitumor Agents ◽  
Design Synthesis ◽  
Biological Studies

Design, synthesis, and molecular docking study of novel quinoline‐based bis ‐chalcones as potential antitumor agents

2021 ◽  
Author(s):  
Daniel Insuasty ◽  
Stephanie García ◽  
Rodrigo Abonia ◽  
Braulio Insuasty ◽  
Jairo Quiroga ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antitumor Agents ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Potential Antitumor

scholarly journals Zinc Complexes with Nitrogen Donor Ligands as Anticancer Agents

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5814
Author(s):  
Marina Porchia ◽  
Maura Pellei ◽  
Fabio Del Bello ◽  
Carlo Santini
Keyword(s):  
Human Body ◽  
Anticancer Agents ◽  
Antitumor Agents ◽  
Physiological Role ◽  
Zinc Complexes ◽  
Redox Activity ◽  
Donor Ligands ◽  
Design Synthesis ◽  
Biological Studies ◽  
Ligands Exchange

The search for anticancer metal-based drugs alternative to platinum derivatives could not exclude zinc derivatives due to the importance of this metal for the correct functioning of the human body. Zinc, the second most abundant trace element in the human body, is one of the most important micro-elements essential for human physiology. Its ubiquity in thousands of proteins and enzymes is related to its chemical features, in particular its lack of redox activity and its ability to support different coordination geometries and to promote fast ligands exchange. Analogously to other trace elements, the impairment of its homeostasis can lead to various diseases and in some cases can be also related to cancer development. However, in addition to its physiological role, zinc can have beneficial therapeutic and preventive effects on infectious diseases and, compared to other metal-based drugs, Zn(II) complexes generally exert lower toxicity and offer few side effects. Zinc derivatives have been proposed as antitumor agents and, among the great number of zinc coordination complexes which have been described so far, this review focuses on the design, synthesis and biological studies of zinc complexes comprising N-donor ligands and that have been reported within the last five years.

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