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

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

Current Medicinal Chemistry ◽

10.2174/0929867326666191016151018 ◽

2019 ◽

Vol 26 ◽

Cited By ~ 1

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.

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

Current Topics in Medicinal Chemistry ◽

10.2174/1568026621666210916171015 ◽

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.

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Quantitative Structure-Activity Relationship Model for HCVNS5B inhibitors based on an Antlion Optimizer-Adaptive Neuro-Fuzzy Inference System

Scientific Reports ◽

10.1038/s41598-017-19122-y ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 5

Author(s):

Mohamed Abd Elaziz ◽

Yasmine S. Moemen ◽

Aboul Ella Hassanien ◽

Shengwu Xiong

Keyword(s):

Fuzzy Inference System ◽

Fuzzy Inference ◽

Quantitative Structure Activity Relationship ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Quantitative Structure ◽

Inference System ◽

Structure Activity ◽

Neuro Fuzzy ◽

Relationship Model

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Biological Activity of Trans-Membrane Anion Carriers

Current Medicinal Chemistry ◽

10.2174/0929867325666180309113222 ◽

2018 ◽

Vol 25 (30) ◽

pp. 3560-3576 ◽

Cited By ~ 3

Author(s):

Massimo Tosolini ◽

Paolo Pengo ◽

Paolo Tecilla

Keyword(s):

Biological Activity ◽

Membrane Transport ◽

Anticancer Agents ◽

Biological Effects ◽

Structure Activity Relationship ◽

New Drugs ◽

Activity Relationship ◽

Anion Channels ◽

Cellular Homeostasis ◽

Structure Activity

Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article, an overview of the recent results on the study of aniontransporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived from dysregulation of natural anion channels.

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Triazol: a privileged scaffold for proteolysis targeting chimeras

Future Medicinal Chemistry ◽

10.4155/fmc-2019-0159 ◽

2019 ◽

Vol 11 (22) ◽

pp. 2919-2973 ◽

Cited By ~ 4

Author(s):

Li-Wen Xia ◽

Meng-Yu Ba ◽

Wei Liu ◽

Weyland Cheng ◽

Chao-Ping Hu ◽

...

Keyword(s):

Drug Discovery ◽

Anticancer Activity ◽

Mode Of Action ◽

Critical Analysis ◽

Enzyme Inhibitors ◽

Structure Activity Relationship ◽

Target Protein ◽

Activity Relationship ◽

Structure Activity ◽

Privileged Scaffold

Current traditional drugs such as enzyme inhibitors and receptor agonists/antagonists present inherent limitations due to occupancy-driven pharmacology as the mode of action. Proteolysis targeting chimeras (PROTACs) are composed of an E3 ligand, a connecting linker and a target protein ligand, and are an attractive approach to specifically knockdown-targeted proteins utilizing an event-driven mode of action. The length, hydrophilicity and rigidity of connecting linkers play important role in creating a successful PROTAC. Some PROTACs with a triazole linker have displayed promising anticancer activity. This review provides an overview of PROTACs with a triazole scaffold and discusses its structure–activity relationship. Important milestones in the development of PROTACs are addressed and a critical analysis of this drug discovery strategy is also presented.

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