Molecular Simulation Studies of 3,3'-Diindolylmethane as a Potent MicroRNA-21 Antagonist.

Objective: In recent decades, the overexpression of microRNA-21 (miR-21) is found to be progressively linked with many diseases such as different types of cancers, cardiovascular diseases, and inflammation. Thereby, it has become an attractive target for pharmacological and genetic modulation in various diseases, and also for overcoming the resistance to chemotherapy in several cancers. Here, in this study, the role of molecular therapeutics of 3,3'-diindolylmethane (DIM) has been investigated for its ability to bind with the precursor miRNA as a target of miR-21 (hsa-mir-21), which may alter the catalyzation process of dicer, a RNase III enzyme, involved in miRNA transcription.

Methods: In this context, the present study describes the potential binding and the structure alteration properties of DIM to precursor miR-21 (pre-miR-21) through Molecular Docking and Molecular Dynamics simulation techniques.

Results: As a corollary, DIM formed both non-bonded and covalent interactions with the bases of pre-miR, while covalent interaction with guanine in the 6 position was found to be consensus in molecular dynamics simulation. Furthermore, the stability of both DIM and pre-miR-21 was found to be inversely correlated to each other in binding condition.

Conclusion: This result indicates that DIM can be used in target-based therapy and also as a lead for further development of potent small molecule miRNA antagonist.