Facile Synthesis, Structural Activity Relationship, Molecular Modeling and In Vitro Biological Evaluation of New Urea Derivatives with Incorporated Isoxazole and Thiazole Moieties as Anticancer Agents

2019 ◽  
Vol 4 (34) ◽  
pp. 10113-10121 ◽  
Author(s):  
Farid M. Sroor ◽  
Amr M. Abdelmoniem ◽  
Ismail A. Abdelhamid
Keyword(s):  
Molecular Modeling ◽  
Anticancer Agents ◽  
Biological Evaluation ◽  
Activity Relationship ◽  
Facile Synthesis ◽  
Urea Derivatives ◽  
Structural Activity Relationship

Recent Design and Structure-Activity Relationship Studies on Modifications of DHFR Inhibitors as Anticancer Agents

2019 ◽  
Vol 26 ◽  
Author(s):  
Agnieszka Wróbel ◽  
Danuta Drozdowska
Keyword(s):  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Physicochemical Characterization ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Biological Research ◽  
Structure Activity ◽  
Dhfr Inhibitors

Background: Dihydrofolate reductase (DHFR) has been known for decades as a molecular target for antibacterial, antifungal and anti-malarial treatments. This enzyme is becoming increasingly important in the design of new anticancer drugs, which is confirmed by numerous studies including modelling, synthesis and in vitro biological research. This review aims to present and discuss some remarkable recent advances on the research of new DHFR inhibitors with potential anticancer activity. Methods: The scientific literature of the last decade on the different types of DHFR inhibitors has been searched. The studies on design, synthesis and investigation structure-activity relationship were summarized and divided into several subsections depending on the leading molecule and its structural modification. Various methods of synthesis, potential anticancer activity and possible practical applications as DHFR inhibitors of new chemical compounds were described and discussed. <p> Results: This review presents the current state of knowledge on the modification of known DHFR inhibitors and the structures and searching for over eighty new molecules, designed as potential anticancer drugs. In addition, DHFR inhibitors acting on thymidylate synthase (TS), carbon anhydrase (CA) and even DNA-binding are presented in this paper. <p> Conclusion: Thorough physicochemical characterization and biological investigations it is possible to understand structure-activity relationship of DHFR inhibitors. This will enable even better design and synthesis of active compounds, which would have the expected mechanism of action and the desired activity.

scholarly journals Molecular modeling study, synthesis and biological evaluation of combretastatin A-4 analogues as anticancer agents and tubulin inhibitors

MedChemComm ◽  
2018 ◽  
Vol 9 (2) ◽  
pp. 316-327 ◽  
Author(s):  
Yang Ping Quan ◽  
Li Ping Cheng ◽  
Tian Chi Wang ◽  
Wan Pang ◽  
Fan Hong Wu ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Anticancer Agents ◽  
Hepg2 Cells ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Tubulin Inhibitors ◽  
Molecular Modeling Study ◽  
Synthesis And Biological Evaluation ◽  
Modeling Study

Compound 13a, more effective than CA-4 against HepG2 cells and tubulin, and the proposed binding mode for 13a.

scholarly journals Synthesis and Biological Evaluation of Novel Triple-Modified Colchicine Derivatives as Potent Tubulin-Targeting Anticancer Agents

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 216 ◽  
Author(s):  
Urszula Majcher ◽  
Greta Klejborowska ◽  
Magdalena Kaik ◽  
Ewa Maj ◽  
Joanna Wietrzyk ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Binding Free Energy ◽  
3D Structure ◽  
Human Tumor ◽  
Biological Evaluation ◽  
Energy Estimates ◽  
Colchicine Derivatives ◽  
Mcf 7

Specific modifications of colchicine followed by synthesis of its analogues have been tested in vitro with the objective of lowering colchicine toxicity. Our previous studies have clearly shown the anticancer potential of double-modified colchicine derivatives in C-7 and C-10 positions. Here, a series of novel triple-modified colchicine derivatives is reported. They have been obtained following a four-step strategy. In vitro cytotoxicity of these compounds has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo, and LoVo/DX). Additionally, the mode of binding of the synthesized compounds was evaluated in silico using molecular docking to a 3D structure of β-tubulin based on crystallographic data from the Protein Data Bank and homology methodology. Binding free energy estimates, binding poses, and MlogP values of the compounds were obtained. All triple-modified colchicine derivatives were shown to be active at nanomolar concentrations against three of the investigated cancer cell lines (A549, MCF-7, LoVo). Four of them also showed higher potency against tumor cells over normal cells as confirmed by their high selectivity index values. A vast majority of the synthesized derivatives exhibited several times higher cytotoxicity than colchicine, doxorubicin, and cisplatin.

Current status of novel pyridine fused derivatives as anticancer agents: An insight into future perspectives and structure activity relationship (SAR)

2021 ◽  
Vol 21 ◽  
Author(s):  
Ajay Manaithiya ◽  
Ozair Alam ◽  
Vrinda Sharma ◽  
Mohd. Javed Naim ◽  
Shruti Mittal ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Heterocyclic Ring ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Current Status ◽  
Normal Tissues ◽  
Structure Activity ◽  
Prevalent Disease

: Cancer is a heterogeneous disease characterized by an abnormal and uncontrolled division of the cells leading to tumors that invade the adjacent normal tissues. After cardiovascular diseases, it is the second most prevalent disease accounting for one in every six deaths worldwide. This alarming rate thus, demands an urgent need to investigate more effective drugs to combat the said disease. Oxygen and nitrogen-based heterocyclic compounds have shown remarkable therapeutic activity towards several diseases, including cancer. In this review, we have attempted to summarize the work done in the last decade (2009-2019), highlighting the anticancer activity of pyrido fused five-membered heterocyclic ring derivatives. Additionally, we have focused on seven heterocyclic pyridine fused rings: Imidazopyridine, Triazolopyridine, Pyrrolopyridine, Pyrazolopyridines, Thienopyridine, and Isoxazolopyridine. A total of forty-nine compounds have been studied based on their in-vitro cytotoxic activity and their structure-activity relationship, underlining the anticancer activity of their various pharmacophores and substituents. This review, therefore, aims to draw the attention of the researchers worldwide towards the enormous scope of development of heterocyclic drug compounds, focussing mainly on pyrido fused five-membered heterocyclic rings as anticancer drugs.

scholarly journals Design, Synthesis and Biological Evaluation of a New Series of 1-Aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea Derivatives as Antiproliferative Agents

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2108 ◽  
Author(s):  
Chuanming Zhang ◽  
Xiaoyu Tan ◽  
Jian Feng ◽  
Ning Ding ◽  
Yongpeng Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Urea Derivatives ◽  
Antiproliferative Agents

To discover new antiproliferative agents with high efficacy and selectivity, a new series of 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea derivatives (7a–7t) were designed, synthesized and evaluated for their antiproliferative activity against A549, HCT-116 and PC-3 cancer cell lines in vitro. Most of the target compounds demonstrated significant antiproliferative effects on all the selective cancer cell lines. Among them, the target compound, 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-{4-{{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}thio}phenyl}urea (7i) was identified to be the most active one against three cell lines, which was more potent than the positive control with an IC50 value of 1.53 ± 0.46, 1.11 ± 0.34 and 1.98 ± 1.27 μM, respectively. Further cellular mechanism studies confirmed that compound 7i could induce the apoptosis of A549 cells in a concentration-dependent manner and elucidated compound 7i arrests cell cycle at G1 phase by flow cytometry analysis. Herein, the studies suggested that the 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea skeleton might be regarded as new chemotypes for designing effective antiproliferative agents.

scholarly journals Chloroquine Urea Derivatives: Synthesis and Antitumor Activity in Vitro

2018 ◽  
Vol 68 (4) ◽  
pp. 471-483 ◽  
Author(s):  
Kristina Pavić ◽  
Zrinka Rajić ◽  
Zvonimir Mlinarić ◽  
Lidija Uzelac ◽  
Marijeta Kralj ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Human Cancer Cell ◽  
Urea Derivatives ◽  
Design Synthesis ◽  
Human Cancer Cell Lines ◽  
Lead Compounds ◽  
Insight Into

Abstract In the current paper, we describe the design, synthesis and antiproliferative screening of novel chloroquine derivatives with a quinoline core linked to a hydroxy or halogen amine through a flexible aminobutyl chain and urea spacer. Synthetic pathway leading to chloroquine urea derivatives 4-10 includes two crucial steps: i) synthesis of chloroquine benzotriazolide 3 and ii) formation of urea derivatives through the reaction of compound 3 with the corresponding amine. Testing of antiproliferative activity against four human cancer cell lines revealed that chloroquine urea derivatives 9 and 10 with aromatic moieties show activity at micromolar concentrations. Therefore, these molecules represent interesting lead compounds that might provide an insight into the design of new anticancer agents.

scholarly journals BIOLOGICAL EVALUATION, QSAR AND MOLECULAR MODELING STUDIES OF 2,4-DICHLOROBENZOIC ACID DERIVATIVES AS ANTIMICROBIAL AGENTS

2019 ◽  
pp. 98-105
Author(s):  
SAMRIDHI THAKRAL ◽  
VIKRAMJEET SINGH
Keyword(s):  
Molecular Modeling ◽  
Antimicrobial Agents ◽  
Structural Characteristics ◽  
Docking Simulation ◽  
Biological Evaluation ◽  
Dilution Method ◽  
Bacterial Strains ◽  
Qsar Studies ◽  
Antimicrobial Potential

Objective: The aim of this study was to evaluate 2,4-dichlorobenzoic acid derivatives as antimicrobial agents through in vitro, QSAR and molecular docking studies. Methods: The compounds were subjected to in vitro antimicrobial screening by test tube dilution method and the structural characteristics governing the antimicrobial potential were studied using QSAR methodology. These compounds were also screened for docking simulation to find out binding confirmation of reported compounds with PDB 1aj0 and 5fsa using AutoDock tools and discovery studio. Results: The antimicrobial evaluation data indicated that compounds 13 and 18 were found to be the most effective against all the bacterial strains and Aspergillus niger while compounds 1 and 14 exhibited more antifungal potential against Candida albicans. QSAR studies confirmed the role of molar refractivity and Balaban index (J) as controlling parameters for antimicrobial potential. Molecular modeling study revealed that compounds interact with the active site of PDB by hydrophobic, hydrogen bonding, and Van der Wall interactions. Conclusion: These test compounds were identified as potent candidates for the control of microbial strains tested, and structural relationship with activity may provide valuable information for further design and synthesis of compounds with antimicrobial potential.

New imidazo[1,2-b]pyrazoles as anticancer agents: Synthesis, biological evaluation and structure activity relationship analysis

2014 ◽  
Vol 84 ◽  
pp. 718-730 ◽  
Author(s):  
Sandrine Grosse ◽  
Véronique Mathieu ◽  
Christelle Pillard ◽  
Stéphane Massip ◽  
Mathieu Marchivie ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Structure Activity Relationship ◽  
Biological Evaluation ◽  
Activity Relationship ◽  
Relationship Analysis ◽  
Structure Activity
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