Novel noscapine derivatives as potent anticancer and antiprotozoal agents

Noscapine as an opium alkaloid has several advantages over present anticancer drugs such as low toxicity, safety, high bioactivity, oral administration and unlike other opium alkaloids, noscapine is non-addictive, non-narcotic and non-analgesic [1].

Novel noscapine derivatives were synthesized via Huisgen and Strecker multi-component reactions to achieve the best cytotoxic and antiprotozoal compounds.

The MTT assay was done against MCF7 cell line and results showed that triazole derivatives had substantial lower cell viability comparing with noscapine. According to MTT results and to have a better idea concerning the mechanism of action, the surface plasmon resonance (SPR) analysis was done and the results indicated that there are promising bindings between the selected ligands and tubulin.

Furthermore, the antiparasitic activity of the synthesized compounds was studied against four unicellular protozoa, i.e., Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum. Interestingly, seven isothiocyanate analogues displayed excellent antiparasitic activity against L.donovani with IC₅₀ values between 0.4 -1.0 µM and selectivity indices (SI) ranged from 7.8 to 18.4, comparable to the standard drug miltefosine (IC₅₀ =0.7 μM).

Regarding molecular modeling studies, there was a good compatibility between the calculated and experimental data on both specific cancer and protozoa receptors.

Therefore, noscapine can be considered as an efficient lead compound in medicinal chemistry for drug design studies.

Fig. 1

• References

• 1 Tomar R, Sahni A, Chandra I, Tomar V, Chandra R. Review of noscapine and its analogues as potential anti-cancer drugs. Mini Rev Org Chem 2018; 15: 345-363.