Design, synthesis, molecular docking and ADME studies of novel indole-thiazolidinedione derivatives and their antineoplastic activity as CDK6 inhibitors

Ateş‐Alagöz, Zeynep; Kışla, Mehmet Murat; Karadayı, Fikriye Zengin; Baran, S. A.; Doğan, Tuğba Somay; Mutlu, Pelin

doi:10.1039/d1nj02808a

Cited by 9 publications

(9 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With a binding affinity of −8.6 kcal/mol, molecule 121 displayed hydrogen bonding with Gln149 and Lys147. In addition to that, it showed one hydrogen bond formation with Ile19 and Gly20 (Ates-Alagoz et al, 2021).…”

Section: Cyclin-dependent Kinase 4 (Cdk4)mentioning

confidence: 84%

A comprehensive analysis of the role of molecular docking in the development of anticancer agents against the cell cycle CDK enzyme

SOLANKI¹,

RANA²,

Jha³

et al. 2023

Biocell

View full text Add to dashboard Cite

Cancer is considered one of the most lethal diseases responsible for causing deaths worldwide. Although there have been many breakthroughs in anticancer development, cancer remains the major cause of death globally. In this regard, targeting cancer-causing enzymes is one of the efficient therapeutic strategies. Biological functions like cell cycle, transcription, metabolism, apoptosis, and other depend primarily on cyclin-dependent kinases (CDKs). These enzymes help in the replication of DNA in the normal cell cycle process, and deregulation in the functioning of any CDK can cause abnormal cell growth, which leads to cancer. This review is focused on anticancer drug discovery against cell cycle CDK enzyme using an in silico technique, i.e., molecular docking studies. Molecular docking helps in deciphering the key interactions formed within the inhibitor and the respective enzyme. This concise study provides an overview of the most current in silico research advancements made in the field of anticancer drug discovery. The findings presented in the current review article can help in understanding the nature of inhibitor-target interactions and provide information on the structural and molecular prerequisites for the inhibition of cell cycle CDKs.

show abstract

Section: Cyclin-dependent Kinase 4 (Cdk4)mentioning

confidence: 84%

A comprehensive analysis of the role of molecular docking in the development of anticancer agents against the cell cycle CDK enzyme

SOLANKI¹,

RANA²,

Jha³

et al. 2023

Biocell

View full text Add to dashboard Cite

show abstract

“…The indole‐thiazolidinedione hybrid 34 (IC 50 : 3.14 µM) had comparable anti‐MCF‐7 cell efficacy as vincristine (IC 50 : 1.00 µM) and potentially cause G1 cell‐cycle arrest by specifically suppressing the activity of cyclin‐dependent kinase 6 (CDK6). [ 65 ] Subsequent structural modification elucidated that the introduction of isoxazole could not improve the antiproliferative activity as evidenced by anti‐MCF‐7 potency of hybrid 35 (IC 50 : 14.15 µM) was lower than that of etoposide (IC 50 : 9.80 µM). [ 66 ] Mechanistically, hybrid 35 (IC 50 : 0.44 µM) could inhibit tubulin polymerization effectively, and the inhibition impact was greater compared with that of combretastatin A‐4 (IC 50 : 1.10 µM).…”

Section: Indole/isatin‐azole Hybridsmentioning

confidence: 99%

The anti‐breast cancer potential of indole/isatin hybrids

Wang,

Huang,

Yuan

et al. 2023

Archiv der Pharmazie

View full text Add to dashboard Cite

Breast cancer (BC) is one of the most prevalent malignancies and the major contributor to cancer mortality in women globally, with a high degree of heterogeneity and a dismal prognosis. As drug resistance is responsible for most BC fatalities and advanced BC is currently considered incurable, finding innovative anti‐BC chemotherapeutics is urgently required. Indole and its analog isatin (indole‐1H‐2,3‐dione) are prominent pharmacophores in the development of novel medications, and their derivatives exhibit strong anticancer activities, also against BC. In particular, indole/isatin hybrids exhibit significant potency against BC including multidrug‐resistant forms and excellent selectivity by influencing a variety of biological targets associated with the disease, supplying helpful building blocks for the identification of potential new BC treatment options. This review includes articles from 2020 to the present and provides insights into the in vitro and in vivo anti‐BC potential, molecular mechanisms, and structure–activity relationships (SARs) of indole/isatin hybrids that may be helpful in the development of innovative anti‐BC chemotherapeutics.

show abstract

“…The nonpermeability of BBB signies the molecule theoretically does not have side effects on the central nervous system. 48 Furthermore, the molecule did not inhibit the P-glycoprotein and CYP-450 class of enzymes, thus having a lower chance of corresponding drug interaction. 48 The toxicity of molecules can damage organs and fail in late-stage drug development.…”

Section: Pharmacokinetics and Physicochemical Propertiesmentioning

confidence: 99%

“…48 Furthermore, the molecule did not inhibit the P-glycoprotein and CYP-450 class of enzymes, thus having a lower chance of corresponding drug interaction. 48 The toxicity of molecules can damage organs and fail in late-stage drug development. So the toxicity of Enceleamycin A was evaluated by the pkCSM web tool, where the compound was negative to the Ames test, which assesses the carcinogenic effect.…”

Section: Pharmacokinetics and Physicochemical Propertiesmentioning

confidence: 99%

In vitro anticancer evaluation of Enceleamycin A and its underlying mechanism

Khan,

Pradeep,

Dastager

2023

RSC Adv.

View full text Add to dashboard Cite

show abstract

Design, synthesis, molecular docking and ADME studies of novel indole-thiazolidinedione derivatives and their antineoplastic activity as CDK6 inhibitors

Abstract: Several indole-thiazolidinedione derivatives (9–24) were designed and synthesized as CDK6 inhibitors, and their anticancer activity was probed on the MCF-7 cell line and the effects on gene expression profiles were elucidated.

Cited by 9 publications

References 48 publications

A comprehensive analysis of the role of molecular docking in the development of anticancer agents against the cell cycle CDK enzyme

A comprehensive analysis of the role of molecular docking in the development of anticancer agents against the cell cycle CDK enzyme

The anti‐breast cancer potential of indole/isatin hybrids

In vitro anticancer evaluation of Enceleamycin A and its underlying mechanism

Contact Info

Product

Resources

About