In silico, spectroscopic, and biological insights on annelated pyrrolo[3,2-e]pyrimidines with antiproliferative activity

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Abstract

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.
Lingua originaleEnglish
pagine (da-a)15-26
Numero di pagine12
RivistaLETTERS IN DRUG DESIGN & DISCOVERY
Volume11
Stato di pubblicazionePublished - 2014

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Pyrimidines
Computer Simulation
DNA
Chromomycin A3
Cell Cycle Resting Phase
G1 Phase
Dactinomycin
Circular Dichroism
Tumor Cell Line
Base Pairing
Cell Cycle
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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title = "In silico, spectroscopic, and biological insights on annelated pyrrolo[3,2-e]pyrimidines with antiproliferative activity",
abstract = "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.",
author = "Giampaolo Barone and Almerico, {Anna Maria} and Carla Gentile and Antonino Lauria and Giuseppe Gennaro and Annamaria Martorana and Alessio Terenzi",
year = "2014",
language = "English",
volume = "11",
pages = "15--26",
journal = "LETTERS IN DRUG DESIGN & DISCOVERY",
issn = "1570-1808",

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TY - JOUR

T1 - In silico, spectroscopic, and biological insights on annelated pyrrolo[3,2-e]pyrimidines with antiproliferative activity

AU - Barone, Giampaolo

AU - Almerico, Anna Maria

AU - Gentile, Carla

AU - Lauria, Antonino

AU - Gennaro, Giuseppe

AU - Martorana, Annamaria

AU - Terenzi, Alessio

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10447/97023

M3 - Article

VL - 11

SP - 15

EP - 26

JO - LETTERS IN DRUG DESIGN & DISCOVERY

JF - LETTERS IN DRUG DESIGN & DISCOVERY

SN - 1570-1808

ER -