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.

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.

One-pot green synthesis of acridine alkaloid derivatives and screening of in vitro anticancer activity against Cdc25b and SHP1

2020 ◽  
Vol 17 ◽  
Author(s):  
Hao Li ◽  
Buer Song ◽  
Mamtimin Mahmut ◽  
Mukhtar Imerhasan
Keyword(s):  
Green Synthesis ◽  
Anticancer Activity ◽  
Inhibitory Activity ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
One Pot ◽  
Structure Activity ◽  
Dna 2 ◽  
Acridone Derivatives

Aims: To develop of anticancer active pharmaceutical intermediates. Background: Acridone derivatives possesses wide range of pharmacological activities:1) intercalate DNA 2) form covalent bond with DNA. Objective: To Screening of in vitro anticancer activity against Cdc25b and SHP1 of new acridone derivatives and preliminary study on structure-activity relationship. Materials and Methods: Synthesis of new acridone derivatives and in vitro evaluation of their anticancer activity on Cdc25b and SHP1. Natural products that contain acridine structures, such as cystodytin A and acronycine, are isolated from certain marine (tunicates & ascidians, sponges, sea anemones) and plant (bark of Australian scrub ash tree) species. Herein, we report the efficient one-pot green synthesis of twelve novel 3,4-dihydro-1 (2H) acridone derivatives, using montmorillonite K10 as the catalyst and iron/citric acid in water. Also, their inhibitory activity against Cdc25B and SHP1 is examined, in which specific derivatives show enhanced inhibitory activity compared to others. Results and Discussion: Starting from 2-nitrobenzaldehyde derivatives and 1, 3-cyclohexanedione derivatives, twelve new acridone derivatives were prepared and exhibited substantial anticancer activity against Cdc25b and SHP1 cells. Conclusion: Preliminary studies of the structure-activity relationship have shown the influence of the structural parameters and, in particular, the nature of the substituent on aromatic ring structure and cyclohexanone. Other: Further study on structure-activity relationship.

scholarly journals Synthesis, Anticancer Evaluation and Structure-Activity Analysis of Novel (E)- 5-(2-Arylvinyl)-1,3,4-oxadiazol-2-yl)benzenesulfonamides

2020 ◽  
Vol 21 (6) ◽  
pp. 2235
Author(s):  
Krzysztof Szafrański ◽  
Jarosław Sławiński ◽  
Łukasz Tomorowicz ◽  
Anna Kawiak
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Human Tumor ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Structure Activity ◽  
Hela Cell Lines ◽  
Hct 116 ◽  
Mcf 7

To learn more about the structure–activity relationships of (E)-3-(5-styryl-1,3,4-oxadiazol-2-yl)benzenesulfonamide derivatives, which in our previous research displayed promising in vitro anticancer activity, we have synthesized a group of novel (E)-5-[(5-(2-arylvinyl)-1,3,4-oxadiazol-2-yl)]-4-chloro-2-R1-benzenesulfonamides 7–36 as well as (E)-4-[5-styryl1,3,4-oxadiazol-2-yl]benzenesulfonamides 47–50 and (E)-2-(2,4-dichlorophenyl)-5-(2-arylvinyl)-1,3,4-oxadiazols 51–55. All target derivatives were evaluated for their anticancer activity on HeLa, HCT-116, and MCF-7 human tumor cell lines. The obtained results were analyzed in order to explain the influence of a structure of the 2-aryl-vinyl substituent and benzenesulfonamide scaffold on the anti-tumor activity. Compound 31, bearing 5-nitrothiophene moiety, exhibited the most potent anticancer activity against the HCT-116, MCF-7, and HeLa cell lines, with IC50 values of 0.5, 4, and 4.5 µM, respectively. Analysis of structure-activity relationship showed significant differences in activity depending on the substituent in position 3 of the benzenesulfonamide ring and indicated as the optimal meta position of the sulfonamide moiety relative to the oxadizole ring. In the next stage, chemometric analysis was performed basing on a set of computed molecular descriptors. Hierarchical cluster analysis was used to examine the internal structure of the obtained data and the quantitative structure–activity relationship (QSAR) analysis with multiple linear regression (MLR) method allowed for finding statistically significant models for predicting activity towards all three cancer cell lines.

Designing new iridium(iii) arene complexes of naphthoquinone derivatives as anticancer agents: a structure–activity relationship study

2017 ◽  
Vol 46 (7) ◽  
pp. 2339-2349 ◽  
Author(s):  
Leila Tabrizi ◽  
Hossein Chiniforoshan
Keyword(s):  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Arene Complexes ◽  
Structure Activity ◽  
Relationship Study

A series of iridium(iii) arene complexes of naphthoquinone derivatives have been synthesized and investigated for their suitability as potential anticancer drugs.

scholarly journals Structure-Activity Relationship for Fe(III)-Salen-Like Complexes as Potent Anticancer Agents

2014 ◽  
Vol 2014 ◽  
pp. 1-10
Author(s):  
Zahra Ghanbari ◽  
Mohammad R. Housaindokht ◽  
Mohammad Izadyar ◽  
Mohammad R. Bozorgmehr ◽  
Hossein Eshtiagh-Hosseini ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Fuzzy Inference ◽  
Statistical Significance ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Geometrical Parameters ◽  
Nonlinear Method ◽  
Inference System ◽  
Structure Activity

Quantitative structure activity relationship (QSAR) for the anticancer activity of Fe(III)-salen and salen-like complexes was studied. The methods of density function theory (B3LYP/LANL2DZ) were used to optimize the structures. A pool of descriptors was calculated: 1497 theoretical descriptors and quantum-chemical parameters, shielding NMR, and electronic descriptors. The study of structure and activity relationship was performed with multiple linear regression (MLR) and artificial neural network (ANN). In nonlinear method, the adaptive neuro-fuzzy inference system (ANFIS) was applied in order to choose the most effective descriptors. The ANN-ANFIS model with high statistical significance (R2train=0.99, RMSE = 0.138, andQ2LOO=0.82) has better capability to predict the anticancer activity of the new compounds series of this family. Based on this study, anticancer activity of this compound is mainly dependent on the geometrical parameters, position, and the nature of the substituent of salen ligand.

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