Discovery of Novel HSP27 Inhibitors as Prospective Anti-Cancer Agents Utilizing Computer-Assisted Therapeutic Discovery Approaches

Haruna Isiyaku Umar; Adeola Temitayo Ajayi; Nobendu Mukerjee; Abdullahi Tunde Aborode; Mohammad Mehedi Hasan; Swastika Maitra; Ridwan O Bello; Hafsat O Alabere; Afees A Sanusi; Olamide O Awolaja; Mohammed M Alshehri; Prosper O Chukwuemeka; Nada H Aljarba; Saad Alkahtani; Sumira Malik; Athanasios Alexiou; Arabinda Ghosh; Md Habibur Rahman

doi:10.3390/cells11152412

Discovery of Novel HSP27 Inhibitors as Prospective Anti-Cancer Agents Utilizing Computer-Assisted Therapeutic Discovery Approaches

Cells. 2022 Aug 4;11(15):2412. doi: 10.3390/cells11152412.

Authors

Haruna Isiyaku Umar^{1

2}, Adeola Temitayo Ajayi^{1

2}, Nobendu Mukerjee^{3

4}, Abdullahi Tunde Aborode⁵, Mohammad Mehedi Hasan⁶, Swastika Maitra⁷, Ridwan O Bello^{2

8}, Hafsat O Alabere^{2

9}, Afees A Sanusi¹⁰, Olamide O Awolaja¹, Mohammed M Alshehri¹¹, Prosper O Chukwuemeka^{2

8}, Nada H Aljarba¹², Saad Alkahtani¹³, Sumira Malik¹⁴, Athanasios Alexiou¹⁵, Arabinda Ghosh¹⁶, Md Habibur Rahman¹⁷

Affiliations

¹ Department of Biochemistry, Federal University of Technology, Akure PMB 704, Nigeria.
² Computer-Aided Therapeutic Discovery and Design Group, FUTA, Akure PMB 704, Nigeria.
³ Department of Microbiology, Ramakrishna Mission Vivekananda Centenary College, Kolkata 700118, India.
⁴ Department of Health Sciences, Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia.
⁵ Healthy Africans Platform, Research and Development, Ibadan 200001, Nigeria.
⁶ Department of Biochemistry and Molecular Biology, Faculty of Life Science, Mawlana Bhashani Science and Technology University, Tangail 1902, Bangladesh.
⁷ Department of Microbiology, Adamas University, Kolkata 222001, India.
⁸ Department of Biotechnology, Federal University of Technology, Akure 340252, Nigeria.
⁹ Department of Microbiology, Federal University of Technology, Akure 340252, Nigeria.
¹⁰ Department of Chemistry, Federal University of Technology, Akure 340252, Nigeria.
¹¹ Pharmaceutical Care Department, Ministry of National Guard-Health Affairs, Riyadh 11426, Saudi Arabia.
¹² Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
¹³ Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
¹⁴ Amity Institute of Biotechnology, Amity University Jharkhand, Ranchi 834001, India.
¹⁵ Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia.
¹⁶ Microbiology Division, Department of Botany, Gauhati University, Guwahati 781014, India.
¹⁷ Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju 26426, South Korea.

Abstract

Heat shock protein 27 (HSP27) is a protein that works as a chaperone and an antioxidant and is activated by heat shock, environmental stress, and pathophysiological stress. However, HSP27 dysregulation is a characteristic of many human cancers. HSP27 suppresses apoptosis and cytoskeletal reorganization. As a result, it is recognized as a critical therapeutic target for effective cancer therapy. Despite the effectiveness of multiple HSP27 inhibitors in pre-clinical investigations and clinical trials, no HSP27 inhibitor has progressed to the anticancer phase of the development. These difficulties have mostly been attributable to existing anticancer therapies' inability to target oncogenic HSP27. Highly selective HSP27 inhibitors with higher effective-ness and low toxicity led to the development of combination techniques that include computer-aided assisted therapeutic discovery and design. This study emphasizes the most recent results and roles of HSP27 in cancer and the potential for utilizing an anticancer chemical database to uncover novel compounds to inhibit HSP27.

Keywords: HSP27 inhibitor; anti-cancer agent; anti-cancer resistance; cancer therapy; computer-assisted therapeutic discovery; molecular docking.

Publication types

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

MeSH terms

Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Apoptosis
Computers
HSP27 Heat-Shock Proteins / metabolism
Humans
Neoplasms* / drug therapy
Neoplasms* / metabolism

Substances

Antineoplastic Agents
HSP27 Heat-Shock Proteins

Grants and funding

This work was funded by the Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2022R62), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. Researchers Supporting Project number (RSP-2021/26), King Saud University, Riyadh, Saudi Arabia.