Bioactive fluorenes. Part IV: Design, synthesis, and a combined in vitro, in silico anticancer and antibacterial evaluation of new fluorene-heterocyclic sulfonamide conjugates

• Published in: Journal of molecular structure 2021-12, Vol.1246, p.131232, Article 131232
• Main Authors: Hussein, Essam M., Malik, M. Shaheer, Alsantali, Reem I., Asghar, Basim H., Morad, Moataz, Ansari, Mohammad Azam, Jamal, Qazi Mohammad Sajid, Alsimaree, Abdulrahman A., Abdalla, Ashraf N., Algarni, Alanood S., Jassas, Rabab S., Altass, Hatem M., Ahmed, Saleh A.
• Format: Article
• Language: English
• Subjects: ADME properties; Anticancer; Apoptosis inducers; Fluorene; Heterocycles; Sulfonamides
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.131232

A series of new fluorene-heterocyclic sulfonamide conjugates were designed and synthesized as potential anticancer agents. In the design of the conjugates, heterocyclic ring systems were utilized for a plausible amplification of bioactivity. The new fluorene-based conjugates were thoroughly characterized and evaluated for antibacterial and anticancer activity against selected bacterial strains and cancer cell lines. The conjugate 8 g, with a 4,6-dimethyl-pyrimidinyl group, exhibited excellent cytotoxicity and selectivity index of 5.6 µM (IC50) and 10.14, respectively, against HCT-116 cancer cell line, which was comparable and superior to standard doxorubicin. Additional clonogenicity, cell migration, and apoptosis induction assays demonstrated that the conjugate 8 g effectively inhibits the colony forming and cell migratory ability of HCT-116 cancer cells with significant apoptosis induction. Moreover, in silico analysis was carried out to understand their binding affinity at the DHPS receptor and all the analyzed conjugates exhibited superior or similar affinity towards the target protein compared to sulfamerazine drug, which was used as control. Additionally, the ADME pharmacokinetics predictions, along with drug likeliness properties, were also investigated. [Display omitted]