Abstract
As part of the research endeavors to combat cancer, a non-symmetric bis-isatin derivative (compound 3) was synthesized and showed a significant anti-proliferative potency. The current study provides a comprehensive characterization of the interaction of compound 3 with the drug-transporting protein bovine serum albumin (BSA) via the use of spectroscopic tools along with molecular docking studies. Fluorescence spectral measurements showed that the BSA intrinsic fluorescence can be significantly quenched by the addition of compound 3 and the formation of a non-fluorescent complex. Further measurements revealed a static type of quenching with Stern–Volmer and Linweaver–Burk constants of 105. The thermodynamic parameters of the binding were calculated to be ΔS° 105.09 ± 5.32 with ΔH° of −0.72 ± 0.71 and negative ΔG° values. In addition, synchronous fluorescence and 3D fluorescence spectroscopy suggested that compound 3 did not induce conformational changes in BSA. Site competition experiments revealed that compound 3 competes with warfarin within the BSA binding domain (Sudlow site I). This was further confirmed by the molecular docking results showing a binding energy of −25.93 kJ/mol for compound 3-BSA. Hence, the observed results in the present study assumed that the compound 3-BSA binding is spontaneous, involving electrostatic forces and hydrogen bonding.
Highlights
Cancer is one of the most serious global health problems, constituting the second major cause of death worldwide [1]
The current study focused on the synthesis of a new highly active anti-proliferative non-symmetric
The current study focused on the synthesis of a new highly active anti-proliferative non-symmetric bis-isatin derivative
Summary
Cancer is one of the most serious global health problems, constituting the second major cause of death worldwide [1]. The development of new, safe, and effective agents for the management of cancer is still a challenge. Isatin (1H-indole-2,3-dione) is an endogenous compound in certain organisms and it was discovered in 1988 [2]. It received considerable attention in the medicinal arena because it is included in a number of bioactive heterocyclic compounds with diverse pharmacological profiles [3,4,5,6,7,8]. A representative example of an already developed isatin-based anticancer drug is sunitinib (I, SutentTM, Pfizer, Inc. New York, NY, USA, Figure 1), which was granted FDA approval in 2006 as an orally active
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
