Background: At present, ‘pharmaco-epigenomics’ constitutes the hope in cancer treatment owing to
epigenetic deregulation- a reversible process and playing a role in malignancy.
Objective: Chemotherapy has many limitations like host-tissue toxicity, drug resistance. Hence, it is imperative
to unearth targets to better treat cancer. Here, we intend to repurpose a set of our previously synthesized
difluorinated Propanediones (PR) as Histone lysine Methyltransferase inhibitors (HMTi).
Methods: The cell lines of leukemic origin viz. histiocytic lymphoma (U937) and acute T-cell leukemia
(JURKAT) were treated with PR-1 to 7 after docking studies with active pocket of HMT. The cell cycle analysis,
in vitro methylation and cell proliferation assays were carried out to delineate their physiological role.
Results: A small molecule PR-4, at 1 and 10µM, has shown to alter the methylation of histone H3 and H4 in
both cell lines. Also, treatment shows an increase in G2/M population and a subsequent decrease in the G0/G1
population in U937. In JURKAT, an increase in both G2/M and S phase population was observed. The sub-G1
population showed a steady rise with increase in dose and prolonged time intervals in U937 and JURKAT cell
lines. In SRB assay, the PR showed a cell growth of 42.6 and 53.4% comparable to adriamycin; 44.5 and 53.2%
in U937 and JURKAT, respectively. The study suggests that PR-4 could emerge as a potential HMT inhibitor.
Conclusion: The molecule PR-4 could be a lead in developing more histone lysine methyltransferases inhibitors
with potential to be pro-apoptotic agents.