Abstract
The nuclear enzyme Poly [ADP-ribose] polymerase 1 (PARP-1) facilitates DNA damage repair which is essential for maintaining genome integrity. The PARP-1 has been touted as an important target for the anticancer therapeutic development as it is overexpressed in various forms of cancer. Several drugs have been approved, and many are under investigation to potentially target PARP-1 and inhibit cancer growth. Of late, anticancer drug development has witnessed a tremendous shift toward natural compounds because of the side effects of conventional therapies. In this study, an attempt has been made to identify the bioactive compounds of Ficus sp. that can potentially bind and inhibit PARP-1 activity by using molecular docking approach. For this purpose, 46 compounds have been retrieved from the IMPPAT database and filtered for their pharmacokinetic properties using Lipinski's Rule of five. The screened compounds were then subjected to docking-based virtual screening using PyRx software, and finally, a total of eight compounds were selected based on their binding affinity towards PARP-1. The interactions of these ligands with PARP-1 were further studied using site-specific molecular docking. These ligands showed strong interaction via several hydrogen bonds and hydrophobic interactions with PARP-1 and had low inhibitory constant (Ki). Based on these findings, it is evident that the bioactive compounds derived from Ficus sp. can be considered as potential anticancer drug candidates. However, further studies in different in vitro and in vivo models would corroborate the inhibitory activity of the ligands targeting PARP-1.