3-Chloro-3-methyl-2,6-diarylpiperidin-4-ones as Anti-Cancer Agents: Synthesis, Biological Evaluation, Molecular Docking, and In Silico ADMET Prediction

Arulraj Ramalingam; Nurulhuda Mustafa; Wee Joo Chng; Mouna Medimagh; Sivakumar Sambandam; Noureddine Issaoui

doi:10.3390/biom12081093

3-Chloro-3-methyl-2,6-diarylpiperidin-4-ones as Anti-Cancer Agents: Synthesis, Biological Evaluation, Molecular Docking, and In Silico ADMET Prediction

Biomolecules. 2022 Aug 8;12(8):1093. doi: 10.3390/biom12081093.

Authors

Arulraj Ramalingam¹, Nurulhuda Mustafa², Wee Joo Chng^{2

3

4}, Mouna Medimagh⁵, Sivakumar Sambandam^{6

7}, Noureddine Issaoui⁵

Affiliations

¹ Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore.
² Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
³ Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
⁴ Department of Haematology-Oncology, National University Cancer Institute of Singapore, National University Health System, Singapore 119228, Singapore.
⁵ Laboratory of Quantum and Statistical Physics (LR18ES18), Faculty of Sciences, University of Monastir, Monastir 5079, Tunisia.
⁶ Research and Development Centre, Bharathiar University, Coimbatore 641046, India.
⁷ BPJ College of Arts and Science, Kozhai, Srimushnam 608703, India.

Abstract

Piperidine pharmacophore-containing compounds have demonstrated therapeutic efficacy against a range of diseases and are now being investigated in cancer. A series of 3-chloro-3-methyl-2,6-diarylpiperidin-4-ones, compounds (I-V) were designed and synthesized for their evaluation as a potential anti-cancer agent. Compounds II and IV reduced the growth of numerous hematological cancer cell lines while simultaneously increasing the mRNA expression of apoptosis-promoting genes, p53 and Bax. Molecular docking analyses confirmed that compounds can bind to 6FS1, 6FSO (myeloma), 6TJU (leukemia), 5N21, and 1OLL (NKTL). Computational ADMET research confirmed the essential physicochemical, pharmacokinetic, and drug-like characteristics of compounds (I-V). The results revealed that these compounds interact efficiently with active site residues and that compounds (II) and (V) can be further evaluated as potential therapeutic candidates.

Keywords: computational ADMET; leukemia; lymphoma; molecular docking calculation; myeloma; piperidin-4-ones.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / chemistry
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents

Grants and funding

This research and APC was funded by the National Research Foundation Singapore and the Singapore Ministry of Education under the Research Centers of Excellence initiative at the Cancer Science Institute of Singapore.