Background:
Modified nucleosides established a prime role as therapeutic drugs.
Objective:
Design and synthesis of novel truncated carbocyclic nucleoside with modified nucleobases and
evaluation of their anticancer properties.
Methods:
Novel truncated carbocyclic nucleoside analogues were synthesized from a versatile starting material
D-ribose. The synthetic route includes stereoselective Grignard reaction, Wittig olefination, ring closing metathesis,
double bond hydrogenation and Mitsunobu nucleobase condensation as the key steps. Cytotoxicity was
measured using MTT assay in breast cancer cell lines (MCF7 and MDA-MB-231), ovarian cancer cell lines
(IGROV1 and OVCAR8).
Result & Conclusion:
The synthesized compounds were characterized using spectroscopy techniques. The
synthesized compounds induced cytotoxicity in breast cancer cell lines (MCF7 and MDA-MB-231), ovarian
cancer cell lines (IGROV1 and OVCAR8) while minimal effect on primary cell line. Among the eight analogues,
1b and 1d showed the highest cytotoxicity effect and induced autophagy mode of cell death. These compounds
induced autophagy by inactivating AKT and mTOR pathway. In addition, PARP1 was found to be stabilized
upon treatment with compound 1b and 1d and is one of the known markers associated with induction of autophagy
through the AMPK/mTOR pathway after DNA damage. Taken together, these results suggest that compounds
1b and 1d inhibit cancer cell proliferation through mTOR inactivation-mediated induction of autophagy.
In view of the potent anticancer activity of the D-arabino-configured cytosine nucleoside (ara-C), apioarabinofuranosyl pyrimidine nucleosides were designed and synthesized from D-ribose as starting material. The synthetic strategy signifies that tosylation followed by in situ cyclization, one-pot controlled oxidative cleavage and acetylation by Pb (OAc) 4 , stereoselective nucleobase condensation, inversion of hydroxyl group and uracil group converted to cytosine as the key steps. Synthesized apioarabinofuranosyl pyrimidine nucleosides were tested using breast, colon, and ovarian cancer cell lines. However, only compound 19a, 19b, and 22b have a moderate growth-suppressive effect against the luminal A breast cancer cell line MCF7. K E Y W O R D S 2, 2 0 -anhyrouridine, apioarabinofurnosyl pyrimidines, apio nucleosides, cytotoxic activity, D-ribose, Vorbrüggen base condensation
A convenient and diverse common synthetic strategy was developed for total synthesis of conduritol‐E, allo‐inositol, talo‐quercitol, and formal synthesis of palitantin from the common polyhydroxylated cyclohexenol intermediate, which was synthesized from readily available D‐ribose. The synthetic avenue includes Barbier allylation, RCM reaction, and oxidative diol cleavage as key steps.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.