Biological Evaluation and Chloroplast Genome Analysis of Western Himalayan Artemisia L

Abstract

Artemisia species have taken much attention as they produce significant antimalarial drug (artemisinin). Beyond malaria, artemisinin along with dihydroartemisinin derivatives are famed for their promising anticancer and antiviral activities. Earlier, triazole functionalized dihydroartemisin derivatives has been reported with enhanced therapeutic prospective. Herein, we newly synthesized fused and 1, 5-disubstituted 1, 2, 3-triazole dihydroartemisinin derivatives in one step, applying the new triazolization methodology. These previously unexplored compounds after characterization were investigated for the anti-HIV (Human Immunodeficiency Virus) capability. Interestingly, three compounds were found potent with IC50 (half maximal inhibitory concentration) values ranging from 1.34 to 2.65 μM. Moreover, we synthesized three series of aza-artemisinin derivatives, characterized and evaluated their anticancer potential. Synthesis of first series of compounds were started from propargyl derivatives of 11-aza-artemisinin and variety of azides followed by copper (I)-catalyzed azide alkyne cycloaddition reaction or click reaction, whereas synthesis of the rest two series of compounds were started from enolizable ketones and primary amines linked to artemisinin followed by triazolization reaction. In vitro evaluation of twenty three derivatives of artemisinin revealed that nine compounds exhibited anti proliferative activity, among which compound 5d proved the most promising inhibiting the growth of CEM and HeLa cancer cells with IC50 values of 0.92 and 1.2 μM, respectively. The present study also investigated the ethno medicinal importance of leaves and stem of Artemisia scoparia and Artemisia brevifolia extracted in various solvents. Qualitative phytochemical screening of both plants confirmed the presence of steroids, sterols, alkaloids, flavonoids, saponins, terpenoids, glycosides, vi tannins, and phenols. Comparative investigation revealed presence of total phenolic and flavonoid content in various concentrations among stem and leaves based on solvents used. Both plants exhibited significant radical scavenging prospective. Cytotoxic potential was shown for HeLa, Hep2, Huh-7 and MCF-7 cancer cell lines. Both plants depicted antiinflammatory activity against MH7A cell line better than standard drug Dexamethasone. Displaying antibacterial and Urease inhibitory potential both plants are strong candidate for active compounds isolation. Further, complete chloroplast genome sequence of Artemisia scoparia is reported in order to resolve taxonomic discrepancies in genus Artemisia. Features including oligonucleotide repeats, amino acid frequencies, microsatellites, codon usage and RNA editing sites of chloroplast genome along with 114 unique genes for tRNA, rRNA and protein coding sequence were identified. Moreover, mutational hotspots were recognized that will help resolve taxonomic discrepancies by developing cost effective molecular markers. Phylogenetic relationship tree was reconstructed for genus Artemisia hence strengthening the previous findings of monophyletic genera. These studies provide basis for deep understanding of pharmacological and taxonomic authentication of Artemisia species.