Green Synthesis, Experimental and Theoretical Studies to Discover Novel Binders of Exosomal Tetraspanin CD81 Protein

Krishnan Anand; Faez I Khan; Thishana Singh; Palani Elumalai; Chandrasekaran Balakumar; Dhanaraj Premnath; Dakun Lai; Anil A Chuturgoon; Muthupandian Saravanan

doi:10.1021/acsomega.0c01166

Green Synthesis, Experimental and Theoretical Studies to Discover Novel Binders of Exosomal Tetraspanin CD81 Protein

ACS Omega. 2020 Jul 16;5(29):17973-17982. doi: 10.1021/acsomega.0c01166. eCollection 2020 Jul 28.

Authors

Krishnan Anand¹, Faez I Khan², Thishana Singh³, Palani Elumalai⁴, Chandrasekaran Balakumar⁵, Dhanaraj Premnath⁶, Dakun Lai², Anil A Chuturgoon⁷, Muthupandian Saravanan⁸

Affiliations

¹ Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences and National Health Laboratory Service, University of the Free State, Bloemfontein 9300, South Africa.
² School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu 610054, PR China.
³ Faculty of Agriculture, Engineering and Science, School of Chemistry and Physics, University of Kwazulu-Natal, Westville Campus, Durban 4013, South Africa.
⁴ Science Department, Texas A&M University at Qatar, Texas A&M Engineering Building, Education City, P.O. Box 23874, Doha 0000, Qatar.
⁵ Faculty of Pharmacy, Philadelphia University,a P.O. Box 1, Amman 19392, Jordan.
⁶ Department of Biotechnology, School of Agriculture and Biosciences, Karunya Institute of Technology and Science, Karunya Nagar, Coimbatore 641114, India.
⁷ Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban 4000, South Africa.
⁸ Department of Microbiology and Immunology, Division of Biomedical Sciences, School of Medicine, College of Health Sciences, Mekelle University, Mekelle 1871, Ethiopia.

Abstract

A new class of benzothiazole-appended quinoline derivatives (6-8) was synthesized via one-pot TPGS micellar-mediated acid-catalyzed nucleophilic addition, followed by aerobic oxidative cyclization of 3-formylquinoline-2-one (2), 3-formylquinoline-2-thione (3), and 2-azidoquinoline-3-carbaldehyde (4) individually with 2-amino thiophenol (5). The structures of the prepared compounds were confirmed using suitable spectroscopic methods complemented with single-crystal X-ray diffraction analysis. Time-dependent density functional theory-based optimization of molecular structures, bond lengths, bond angles, HOMO-LUMO energy gaps, and molecular electrostatic potential maps was theoretically computed at the B3LYP/6-311++g(d) level. The molecular docking studies recommended that 6-8 bound to the active site cavity of CD81 effectively with the binding energies of -6.9, -6.3, and -6.5 kcal mol^-1, respectively. Further, MD simulation studies of compound 6 suggested that the binding resulted in the stabilization of the CD81 molecule. Thus, all theoretical predictions associated with the experimental verifications motivated to discover novel approaches for cancer therapy.