Rational Design and Synthesis of Naphthalene Diimide Linked Bis-Naphthalimides as DNA Interactive Agents

M Shaheer Malik; Syed Farooq Adil; Ziad Moussa; Hatem M Altass; Ismail I Althagafi; Moataz Morad; Mohammad Azam Ansari; Qazi Mohammad Sajid Jamal; Rami J Obaid; Abdulrahman A Al-Warthan; Thokhir B Shaik; Saleh A Ahmed

doi:10.3389/fchem.2021.630357

Rational Design and Synthesis of Naphthalene Diimide Linked Bis-Naphthalimides as DNA Interactive Agents

Front Chem. 2021 Mar 10:9:630357. doi: 10.3389/fchem.2021.630357. eCollection 2021.

Affiliations

¹ Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.
² Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
³ Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates.
⁴ Department of Epidemic Disease Research, Institute for Research & Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia.
⁵ Department of Health Informatics, College of Public Health and Health Informatics, Qassim University, Al Bukayriyah, Saudi Arabia.
⁶ Research on Advanced BioMedical Solutions Pvt Ltd, KPHB, Hyderabad, 500071, India.
⁷ Department of Chemistry, Faculty of Science, Assiut University, 71516, Assiut, Egypt.
⁸ Research Laboratories Unit, Faculty of Applied Science, Umm Al-Qura University, 21955, Makkah, Saudi Arabia.

Abstract

A molecular modeling assisted rational design and synthesis of naphthalene diimide linked bis-naphthalimides as potential DNA interactive agents is described. Chemical templates incorporating naphthalene diimide as a linker in bis-naphthalimide motif were subjected to molecular docking analysis at specific intercalation and telomeric DNA G-quadruplex sites. Excellent results were obtained, which were better than the standards. A short and convenient synthetic route was employed to access these hybrids experimentally, followed by evaluation of their ability to cause thermal denaturation of DNA and cytotoxic properties along with ADME predictions. The obtained results provided useful insights and two potential molecules were identified for further development.

Keywords: DNA interactive; anticancer agents; bis-naphthalimides; molecular modeling; naphthalene diimide.