Computational Screening of Natural Compounds for Identification of Potential Anti-Cancer Agents Targeting MCM7 Protein

Abstract

Minichromosome maintenance complex component 7 (MCM7) is involved in replicative licensing and the synthesis of DNA, and its overexpression is a fascinating biomarker for various cancer types. There is currently no effective agent that can prevent the development of cancer caused by the MCM7 protein. However, on the molecular level, inhibiting MCM7 lowers cancer-related cellular growth. With this purpose, this study screened 452 biogenic compounds extracted from the UEFS Natural Products dataset against MCM protein by using the in silico art of technique. The hit compounds UEFS99, UEFS137, and UEFS428 showed good binding with the MCM7 protein with binding energy values of −9.95, −8.92, and −8.71kcal/mol, which was comparatively higher than that of the control compound ciprofloxacin (-6.50). The hit (UEFS99) with the minimum binding energy was picked for molecular dynamics (MD) simulation investigation, and it demonstrated stability at 30 ns. Computational prediction of physicochemical property evaluation revealed that these hits are non-toxic and have good drug-likeness features. It is suggested that hit compounds UEFS99, UEFS137, and UEFS428 pave the way for further bench work validation in novel inhibitor development against MCM7 to fight the cancers.

High-Throughput Screening and Molecular Dynamics Simulation of Natural Products for the Identification of Anticancer Agents against MCM7 Protein

“…Cancer development is aided by the MCM7 protein, which is linked to tumor cell proliferation. A therapy approach for several human cancers is possible since the protein is extensively expressed during cancer development [ 46 ].…”

“…Cancer development is aided by the MCM7 protein, which is linked to tumor cell proliferation. A therapy approach for several human cancers is possible since the protein is extensively expressed during cancer development [46]. Medicinal plants have changed from fringe to mainstream usage in recent decades, and a growing number of individuals are seeking relief from herbal extracts [47].…”

Ellagic Acid as a Potential Inhibitor against the Nonstructural Protein NS3 Helicase of Zika Virus: A Molecular Modelling Study

“…Similarly, Gahlawat et al (2020) screened inhibitors for the target main protease of SARS CoV-2; they used main protease inhibitors, natural products, and FDA-approved drugs [65]. The active site helps ligands to create enough contact sites to produce excellent interaction with the target protein by maintaining appropriate and desirable catalytic microenvironments [66][67][68][69]. In the ATP binding site of the NS3 helicase, the amino acids Glu231, Arg459, Gln455, Arg202, Glu286, Glu231, and Lys200 play a key role in the interaction with the ligands ellagic acid, hypericin, and pentagalloylglucose.…”

Recent Advances in the Development of Non-PIKKs Targeting Small Molecule Inhibitors of DNA Double-Strand Break Repair

“…However, most recently inhibition of MCM2-7 activity by ciprofloxacin significantly delayed neuroendocrine prostate cancer (NEPC) cell growth and migration in vitro , exhibited potent anti-tumor effects in an NEPC xenograft model, and partially reversed neuroendocrine features ( 229 ). Alshahrani et al identified UEFS99, UEFS137 and UEFS428 as MCM7 inhibitors from the natural compounds databases using in silico computational screening, however further in vitro and in vivo studies are needed to validate target engagement ( 230 ). A furanonaphthoquinone-based small molecule, AS4583 was identified as an MCM2 inhibitor through phenotypic screening and target deconvolution ( 231 ).…”