The in silico COMPARE analysis was performed on 8-[3-(piperidino)propyl]-4,10-dimethyl-9-phenyl-6-
(methylsulfanyl)-3,4-dihydropyrimido[1,2-c]pyrrolo[3,2-e]pyrimidin-2(8H)-one, a compound with promising antiproliferative
activity, previously synthetized and screened against a panel of 60 human tumor cell lines. The results evidenced
that this compound matches the biological properties of Chromomycin A3 and Actinomycin D, known drugs with high
DNA binding affinity. Prompted by such results, a thorough spectroscopic investigation of its DNA aqueous solutions was
performed, with the aim to verify its DNA-binding properties. DNA groove-binding interaction was assigned by UV-vis
spectrophotometric and circular dichroism (CD) titrations. In agreement with the spectroscopic studies, the test compound
has achieved significant cell-cycle perturbation with higher accumulation of cells in G0/G1 phase. Further structure modifications
of the tested compound, has led to its analogue, which showed DNA base-pairs intercalating ability. Molecular
modeling studies on the annelated pyrrolo[3,2-e]pyrimidines tested were in agreement with the biological evaluation.
Keywords: Anticancer drugs, DNA interactive drugs, COMPARE analysis, Annelated pyrrolo-pyrimidines, UV-vis DNA titrations,
Circular Dichroism, Ethidium bromide displacement assay, Cell Cycle.
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