Structural exploration of tetrahydroisoquinoline derivatives as HDAC8 inhibitors through multi-QSAR modeling study

Abstract

Histone deacetylase 8 (HDAC8) is one of the crucial HDACs responsible for influencing the epigenetic functions of the body. Overexpression of HDAC8 is found to be involved in numerous disease conditions such as tumorigenesis, cell proliferation, cancer, viral infections, neuronal disorders and other epigenetic diseases. Therefore, inhibition of HDAC8 is a primary method to combat these diseases. In this article, a multi-QSAR modeling study on tetrahydroisoquinoline derivatives was conducted to identify important contributions of the structural features of these compounds toward HDAC8 inhibition. All these QSAR modeling techniques were individually validated and justified the observations of each other. The results implied that the tetrahydroisoquinoline moiety may be effective as a cap group than as a linker moiety for HDAC8 inhibition. Different substitutions at the tetrahydroisoquinoline scaffold were also found to be crucial in modulating HDAC8 inhibition.

Communicated by Ramaswamy H. Sarma

Keywords:

• HDAC8
• tetrahydroisoquinoline
• 2D QSAR
• Bayesian classification
• CoMFA
• HQSAR

Acknowledgements

Suvankar Banerjee is sincerely grateful to the All India Council for Technical Education (AICTE) New Delhi for awarding a fellowship. Sk. Abdul Amin sincerely acknowledges the Council of Scientific & Industrial Research (CSIR), New Delhi, for awarding the Senior Research Fellowship [FILE NO.: 09/096(0967)/2019-EMR-I, Dated: 01-04-2019].

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Tarun Jha is thankful for the financial support from RUSA 2.0 and UPE Phase II Program of UGC, New Delhi, to Jadavpur University, Kolkata, India.

Notes on contributors

Suvankar Banerjee

Suvankar Banerjee, Nilanjan Adhikari and Sk. Abdul Amin participated in the designing of the research with the guidance of Tarun Jha. Sk. Abdul Amin and Nilanjan Adhikari performed research experiments, analyzed the data and wrote the manuscript. Suvankar Banerjee contributed toward the development analysis of the 2D-QSAR models. Tarun Jha, the mentor, contributed in manuscript preparation and provided valuable guidance throughout the manuscript review.

Nilanjan Adhikari

Suvankar Banerjee, Nilanjan Adhikari and Sk. Abdul Amin participated in the designing of the research with the guidance of Tarun Jha. Sk. Abdul Amin and Nilanjan Adhikari performed research experiments, analyzed the data and wrote the manuscript. Suvankar Banerjee contributed toward the development analysis of the 2D-QSAR models. Tarun Jha, the mentor, contributed in manuscript preparation and provided valuable guidance throughout the manuscript review.

Sk. Abdul Amin

Suvankar Banerjee, Nilanjan Adhikari and Sk. Abdul Amin participated in the designing of the research with the guidance of Tarun Jha. Sk. Abdul Amin and Nilanjan Adhikari performed research experiments, analyzed the data and wrote the manuscript. Suvankar Banerjee contributed toward the development analysis of the 2D-QSAR models. Tarun Jha, the mentor, contributed in manuscript preparation and provided valuable guidance throughout the manuscript review.

Tarun Jha

Suvankar Banerjee, Nilanjan Adhikari and Sk. Abdul Amin participated in the designing of the research with the guidance of Tarun Jha. Sk. Abdul Amin and Nilanjan Adhikari performed research experiments, analyzed the data and wrote the manuscript. Suvankar Banerjee contributed toward the development analysis of the 2D-QSAR models. Tarun Jha, the mentor, contributed in manuscript preparation and provided valuable guidance throughout the manuscript review.