Suresh Palanivel
@tuni.fi
Post Doctoral Researcher/Faculty of Medicine and Health Technology
Tampere University
EDUCATION
August 2022 D.Sc (Tech), Biomedical Science and Engineering Tampere University, Tampere, Finland, Finland
June 2012 Master of Science, Biotechnology, Edinburgh Napier University, Edinburgh, United Kingdom
April 2010 B.Tech, Biotechnology, Kamaraj College of Engineering and Technology, Anna University, Virudhunagar, India
RESEARCH, TEACHING, or OTHER INTERESTS
Cancer Research, Cell Biology, Molecular Biology, Drug Discovery
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Akshaya Murugesan, Saravanan Konda Mani, Ramesh Thiyagarajan, Suresh Palanivel, Atash V. Gurbanov, Fedor I. Zubkov, and Meenakshisundaram Kandhavelu
MDPI AG
The tropomyosin receptor kinase A (TrkA) family of receptor tyrosine kinases (RTKs) emerge as a potential target for glioblastoma (GBM) treatment. Benzenesulfonamide analogs were identified as kinase inhibitors possessing promising anticancer properties. In the present work, four known and two novel benzenesulfonamide derivatives were synthesized, and their inhibitory activities in TrkA overexpressing cells, U87 and MEF cells were investigated. The cytotoxic effect of benzenesulfonamide derivatives and cisplatin was determined using trypan blue exclusion assays. The mode of interaction of benzenesulfonamides with TrkA was predicted by docking and structural analysis. ADMET profiling was also performed for all compounds to calculate the drug likeness property. Appropriate QSAR models were developed for studying structure–activity relationships. Compound 4-[2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl]-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfon-amide (AL106) and 4-[2-(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)hydrazinyl]-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide (AL107) showed acceptable binding energies with the active sites for human nerve growth factor receptor, TrkA. Here, AL106 was identified as a potential anti-GBM compound, with an IC50 value of 58.6 µM with a less toxic effect in non-cancerous cells than the known chemotherapeutic agent, cisplatin. In silico analysis indicated that AL106 formed prominent stabilizing hydrophobic interactions with Tyr359, Ser371, Ile374 and charged interactions with Gln369 of TrkA. Furthermore, in silico analysis of all benzenesulfonamide derivatives revealed that AL106 has good pharmacokinetics properties, drug likeness and toxicity profiles, suggesting the compound may be suitable for clinical trial. Thus, benzenesulfonamide analog, AL106 could potentially induce GBM cell death through its interaction with TrkA and might be an attractive strategy for developing a drug targeted therapy to treat glioblastoma.
Suresh Palanivel, Olli Yli-Harja, and Meenakshisundaram Kandhavelu
Informa UK Limited
Abstract Epidermal growth factor receptors are constitutively overexpressed in breast cancer cells, which in turn stimulate many downstream signaling pathways that are involved in many carcinogenic processes. This makes EGFR a striking target for cancer therapy. This study focuses on the EGFR kinase domain inactivation by novel synthesized indoline derivatives. The compounds used are N-(2-hydroxy-5-nitrophenyl (4’-methyl phenyl) methyl) indoline (HNPMI), alkylaminophenols − 2-((3,4-Dihydroquinolin-1(2H)-yl) (p-tolyl) methyl) phenol (THTMP) and 2-((1, 2, 3, 4-Tetrahydroquinolin-1-yl) (4 methoxyphenyl) methyl) phenol (THMPP). To get a clear insight into the molecular interaction of EGFR and the three compounds, we have used ADME/Tox prediction, Flexible docking analysis followed by MM/GB-SA, QM/MM analysis, E-pharmacophore mapping of the ligands and Molecular dynamic simulation of protein-ligand complexes. All three compounds showed good ADME/Tox properties obeying the rules of drug-likeliness and showed high human oral absorption. Molecular docking was performed with the compounds and EGFR using Glide Flexible docking mode. This showed that the HNPMI was best among the three compounds and had interactions with key residue Lys 721. The protein-ligand complexes were stable when simulated for 100 ns using Desmond software. The interactions were further substantiated using QM/MM analysis and MM-GB/SA analysis in which HNPMI was scored as the best molecule. All the analyses were carried out with a reference molecule—Gefitinib which is a known standard inhibitor of EGFR. Thus, the study elucidates the potential role of the indoline derivatives as an anti-cancer agent against breast cancer by effectively inhibiting EGFR. Communicated by Ramaswamy H. Sarma
Suresh Palanivel, Akshaya Murugesan, Kumar Subramanian, Olli Yli-Harja, and Meenakshisundaram Kandhavelu
Elsevier BV
Suresh Palanivel, Akshaya Murugesan, Olli Yli-Harja, and Meenakshisundaram Kandhavelu
Elsevier BV
Suresh Palanivel, Olli Yli-Harja, and Meenakshisundaram Kandhavelu
Bentham Science Publishers Ltd.
Background and Objective: The present study was carried out to evaluate the anticancer property of an alkylamino phenol derivative -2-((3,4-Dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol) (THTMP) against human breast cancer cells. The cytotoxicity of the THTMP was assessed to know its specificity towards breast cancer cells without affecting the normal cells. Methods: The THTMP was synthesized and the cytotoxicity was assessed by MTT assay, Caspases enzyme activity, DNA fragmentation and FITC/Annexin V, AO/EtBr staining, RT-PCR and QSAR. In addition, ADME analysis was executed to understand the mode of action of THTMP. Results: THTMP showed potential cytotoxic activity against the growth of MCF7 and SK-BR3 cells with the IC50 values of 87.92μM and 172.51μM, respectively. Interestingly, THTMP found to activate caspase 3 and caspase 9 enzymes in cancer cells, which are the key enzymes implicated in apoptosis. THTMP induced apoptosis in which 33% of the cells entered the late apoptotic stage after 24h of treatment. The results also revealed that the apoptotic response could be influenced by the association of THTMP with the Epidermal Growth Factor Receptor (EGFR) mediated inhibition of the Phosphatidylinositol 3-Kinase (PI3K)/S6K1 signaling pathway. In addition, docking was performed to study the binding mode of the THTMP, which shows better interaction with EGFR. The structural elucidation of THTMP by Quantitative Structure-Activity Relationship model (QSAR) and ADMET screening suggested, THTMP as an effective anticancer compound. Conclusion: This work strengthens the potential of a promising drug-like compound, THTMP, for the discovery of anticancer drug against breast cancer.
Suresh Palanivel, Anastasia Zhurina, Phuong Doan, Jerome G. Chandraseelan, Vinoth Kumar Megraj Khandelwal, Fedor I. Zubkov, Kamran T. Mahmudov, Armando J.L. Pombeiro, Olli Yli-Harja, and Meenakshisundaram Kandhavelu
Elsevier BV
Konda Mani Saravanan, Suresh Palanivel, Olli Yli-Harja, and Meenakshisundaram Kandhavelu
Elsevier BV
Jeyalakshmi Kandhavelu, Suresh Palanivel, and Meenakshisundaram Kandhavelu
Bentham Science Publishers Ltd.
HISTORY
Nuclear Hormone Receptors (NHRs) are the most important targets that play vital role in cellular signaling pathways of disease. Regulation of NHRs by using potential non-coding RNAs, miRNA, is clinically important to control a disease. However, the detailed status of miRNA interactions with NHRs remains unclear. Hence, the focus of the present study is to investigate the interface at the genome-wide level in human, mouse and rat using computational biology approach.
OBSERVATIONS
This big-data analysis explored thousands of available miRNAs interactions with the NHRs and the results showed that 11 miRNAs have conserved targets, where six miRNAs are genetically conserved among different species. This implies that both conserved and non-conserved miRNAs have a potential role in NHRs regulation. We found several "Aberrantly Binding miRNAs" (ABMs) that can bind to the target NHR genes. In this study, for human miR-548, rat miR-Let-7 and miR-30, mouse miR-466 are identified as potential ABMs families. We also found the list of genes targeting ABMs.
RESULTS
Specifically, these miRNAs majorly targeted bind nuclear subfamily receptor genes in all studied animal species. ABMs family interaction with NHR genes is favored by AT richness and the length of the gene.
CONCLUSION
Our findings suggest that, specific ABMs family targeting NHRs may act as potential candidates to regulate the downstream signaling pathways.