Searching for anti-glioma activity. Ribonucleoside analogues with modifications in nucleobase and sugar moieties.

Abstract

Several ribonucleoside analogues with modifications in the nucleobase and sugar moiety have been screened for anti-glioma activity in the T98G glioma cell line using cervical (HeLa) cell line as reference human malignant cells, and lung fibroblast (MCR-5) cell line as non-cancerous reference cells. Among the investigated compounds, ribonucleosides containing 6-chloropurine (3), 7-guanine (5) and a pyrrolopyrimidine (18) as nucleobases, show promising anti-glioma activity with good selectivity indices, and can be considered as lead structures for further anti-cancer studies.

7‐(β‐D‐Ribofuranosyl)guanine and its Analogues Modified in the Sugar Portion: Synthesis and Antiglioma Properties

“…We are going to reduce that backlog in the present project, which is limited here to analogs modified in the sugar portion, and in further research, involving modification of the aglycon part. Taking advantage of our unexpected finding, [1] we decided to synthesize and evaluate as antiglioma agents a series of known and novel 7‐regioisomers of guanine nucleosides and its analogs, having guanine 7‐riboside ( 2 ) as the lead structure.…”

“…Recently we have discovered that 7-regioisomer of naturally occurring guanosine (Figure 1; compound 1), i. e. 7-(β-Dribofuranosyl)guanine (2), demonstrated high (IC 50 1.6 μM) and selective anticancer activity in vitro against glioma cell lines T98G (Glioblastoma multiforme). [1] Glioblastomas are exceptionally malignant brain neoplasms, practically incurable at the present state of medicine. This unexpected finding prompted us to look closer at regioisomeric derivatives of naturally occurring nucleosides.…”

Aktywność biologiczna N6-furfuryloadenozyny

“…Naturalnie występujące analogi nukleozydów takie jak: N 6 -izopentenyloadenozyna (iPR), rybozyd kinetyny (KR) oraz N 6 -benzyloadenozyna (BAR) wykazują inhibicję wzrostu i indukcję apoptozy w komórkach nowotworowych [51][52][53][54][55][56][57]. Cytokininy w formie wolnych zasad, takie jak: N 6 -izopentenyloadenina (iP), kinetyna (K) oraz N 6 -benzyloadenina (BA) hamują proliferację komórek białaczkowych NB4, ML-1, U937 oraz powodują różnicowanie ich w dojrzałe granulocyty [58].…”

High PLA2 level is correlated with glioblastoma progression via regulating DNA replication

“…The features of molecular heterogeneity and mutability contribute to the poor response of glioblastoma to conventional DNA‐damaging chemotherapies. Novel therapies, drugs and drug combinations are needed to prolong GBM patient lifespan 6,7 …”