Synthesis of Novel Jusbetonin Analogues and Their Cytotoxicity against Tumor Cell

Abstract

Six novel analogues of bioactive natural indolo[3,2‐b]quinoline alkaloid glycoside jusbetonin were designed and synthesized, employing polyphosphoric acid mediated cyclization and two different amidation strategies on introduction of tetra‐O‐acetyl‐β‐d‐glucosamine to tetracyclic carboxylic acids.

Synthesis and pharmacological characterization of glucopyranosyl-conjugated benzyl derivatives as novel selective cytotoxic agents against colon cancer

“…Deacetylate significantly reduced the anti-tumour activity as observed from compound 9d . Acetyl was helpful to increase the anti-tumour activity via improving liposolubility [ 18 ].…”

“…The key intermediate 1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-D-glucose 4 was prepared from commercially available β-D-glucosamine hydrochoride 1, of which the 2-amino group was converted into azido group via reaction with imidazole-1-sulfonyl azide hydrochloride 2 under basic condition [19,20]. The propargyl-functionalized benzyl 7 was prepared via alkylation of the benzyl alcohol 6 with 3-bromopropyne [18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Coupling of compound 4 with the propargyl-functionalized benzyl 7 in the presence of copper(I) at 100°C with the assistance of microwave irradiation yielded the desired compounds 8a-i.…”

“…In this study, we hypothesized that conjugating the cytotoxic benzyl with a carbohydrate could yield novel cytotoxic compounds with improved cytotoxic selectivity towards cancer cells. A previous study demonstrated that 1,3,4,6-tetra- O -acetyl- d -glucose-conjugated indoloquinoline derivatives exhibited more optimal anti-cancer activities than their deacetylation counterparts [ 18 ]. Similarly, our early work in conjugation of 1,3,4,6-tetra- O -acetyl- d -glucose with organic arsenic compound ( p -APAO) suggested that the presence of four acetyl groups on the β- d -glucose still maintained the cytotoxic activity of the organic arsenic compound [ 17 ].…”

Carbohydrate-conjugated 4-(1,3,2-dithiarsolan-2-yl)aniline as a cytotoxic agent against colorectal cancer

“…In a structural optimization, the replacement of its b-D-glucose with OADG was shown to enhance the cytotoxicity against breast cancer cell line MDA-231. 22 Based on these results, we hypothesized that introducing OADG into organic arsenic compounds such as p-APDTAs may preserve the anticancer effects of organic arsenic compounds while the cytotoxicity toward normal cells can be reduced. Hence, we designed and synthesized OADGconjugated p-APAO analogue (8) and p-APDTAs analogue (9).…”

“…The acetyl protective groups were deemed beneficial in comparison with the unprotected β- d -glucosamine bearing analogues. 22 …”