PMID- 37949265
OWN - NLM
STAT- MEDLINE
DCOM- 20240105
LR  - 20240116
IS  - 1879-0003 (Electronic)
IS  - 0141-8130 (Linking)
VI  - 254
IP  - Pt 3
DP  - 2024 Jan
TI  - Study of nitrogen heterocycles as DNA/HSA binder, topoisomerase inhibitors and 
      toxicological safety.
PG  - 127651
LID - S0141-8130(23)04549-X [pii]
LID - 10.1016/j.ijbiomac.2023.127651 [doi]
AB  - Four new nitrogen-containing heterocyclic derivatives (acridine, quinoline, 
      indole, pyridine) were synthesized and their biological properties were 
      evaluated. The compounds showed affinity for DNA and HSA, with CAIC and CAAC 
      displaying higher binding constants (Kb) of 9.54 x 10(4) and 1.06 x 10(6), 
      respectively. The fluorescence quenching assay (Ksv) revealed suppression values 
      ranging from 0.34 to 0.64 x 10(3) M(-1) for ethidium bromide (EB) and 0.1 to 
      0.34 x 10(3) M(-1) for acridine orange (AO). Molecular docking confirmed the 
      competition of the derivatives with intercalation probes at the same binding 
      site. At 10 muM concentrations, the derivatives inhibited topoisomerase IIalpha 
      activity. In the antiproliferative assays, the compounds demonstrated activity 
      against MCF-7 and T47-D tumor cells and nonhemolytic profile. Regarding toxicity, 
      no acute effects were observed in the embryos. However, some compounds caused 
      enzymatic and cardiac changes, particularly the CAIC, which increased SOD 
      activity and altered heart rate compared to the control. These findings suggest 
      potential antitumor action of the derivatives and indicate that substituting the 
      acridine core with different cores does not interfere with their interaction and 
      topoisomerase inhibition. Further investigations are required to assess possible 
      toxicological effects, including reactive oxygen species generation.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Dos Santos, Jessica Celerino
AU  - Dos Santos JC
AD  - Molecular Biology Laboratory, University of Pernambuco (UPE), Multicampi 
      Garanhuns, Garanhuns, PE 55290-000, Brazil.
FAU - Alves, Josival Emanuel Ferreira
AU  - Alves JEF
AD  - Keizo Asami Immunopathology Laboratory (LIKA), Federal University of Pernambuco, 
      Recife, PE, Brazil.
FAU - de Azevedo, Rafael David Souto
AU  - de Azevedo RDS
AD  - Molecular Biology Laboratory, University of Pernambuco (UPE), Multicampi 
      Garanhuns, Garanhuns, PE 55290-000, Brazil.
FAU - de Lima, Maksuelly Libanio
AU  - de Lima ML
AD  - Molecular Biology Laboratory, University of Pernambuco (UPE), Multicampi 
      Garanhuns, Garanhuns, PE 55290-000, Brazil.
FAU - de Oliveira Silva, Maria Regina
AU  - de Oliveira Silva MR
AD  - Molecular Biology Laboratory, University of Pernambuco (UPE), Multicampi 
      Garanhuns, Garanhuns, PE 55290-000, Brazil.
FAU - da Silva, Josefa Gerlane
AU  - da Silva JG
AD  - Molecular Biology Laboratory, University of Pernambuco (UPE), Multicampi 
      Garanhuns, Garanhuns, PE 55290-000, Brazil.
FAU - da Silva, Jamire Muriel
AU  - da Silva JM
AD  - Department of Pharmacy, Laboratory of Synthesis and Vectorization of Molecules, 
      State University of Paraiba (UEPB), Campus Campina Grande, 58429-500, PB, Brazil.
FAU - de Carvalho Correia, Ana Carolina
AU  - de Carvalho Correia AC
AD  - Molecular Biology Laboratory, University of Pernambuco (UPE), Multicampi 
      Garanhuns, Garanhuns, PE 55290-000, Brazil.
FAU - do Carmo Alves de Lima, Maria
AU  - do Carmo Alves de Lima M
AD  - Chemistry and Therapeutic Innovation Laboratory (LQIT), Department of 
      Antibiotics, Federal University of Pernambuco, Recife, PE, Brazil.
FAU - de Oliveira, Jamerson Ferreira
AU  - de Oliveira JF
AD  - University of International Integration of Afro-Brazilian Lusophony (UNILAB), 
      62790-970 Redencao, CE, Brazil.
FAU - de Moura, Ricardo Olimpio
AU  - de Moura RO
AD  - Department of Pharmacy, Laboratory of Synthesis and Vectorization of Molecules, 
      State University of Paraiba (UEPB), Campus Campina Grande, 58429-500, PB, Brazil.
FAU - de Almeida, Sinara Monica Vitalino
AU  - de Almeida SMV
AD  - Molecular Biology Laboratory, University of Pernambuco (UPE), Multicampi 
      Garanhuns, Garanhuns, PE 55290-000, Brazil; Keizo Asami Immunopathology 
      Laboratory (LIKA), Federal University of Pernambuco, Recife, PE, Brazil; 
      Chemistry and Therapeutic Innovation Laboratory (LQIT), Department of 
      Antibiotics, Federal University of Pernambuco, Recife, PE, Brazil. Electronic 
      address: sinara.monica@upe.br.
LA  - eng
PT  - Journal Article
DEP - 20231108
PL  - Netherlands
TA  - Int J Biol Macromol
JT  - International journal of biological macromolecules
JID - 7909578
RN  - 0 (Topoisomerase Inhibitors)
RN  - 0 (Antineoplastic Agents)
RN  - 9007-49-2 (DNA)
RN  - 0 (Intercalating Agents)
RN  - 0 (Acridines)
SB  - IM
MH  - *Topoisomerase Inhibitors/pharmacology/chemistry
MH  - Structure-Activity Relationship
MH  - Molecular Docking Simulation
MH  - *Antineoplastic Agents/chemistry
MH  - DNA/chemistry
MH  - Intercalating Agents/pharmacology
MH  - Acridines/pharmacology/chemistry
MH  - Cell Proliferation
MH  - Drug Screening Assays, Antitumor
MH  - Molecular Structure
OTO - NOTNLM
OT  - Cancer therapy
OT  - Danio rerio
OT  - N-heteroaromatic
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/11/11 11:42
MHDA- 2024/01/05 06:43
CRDT- 2023/11/10 19:15
PHST- 2023/06/22 00:00 [received]
PHST- 2023/10/19 00:00 [revised]
PHST- 2023/10/23 00:00 [accepted]
PHST- 2024/01/05 06:43 [medline]
PHST- 2023/11/11 11:42 [pubmed]
PHST- 2023/11/10 19:15 [entrez]
AID - S0141-8130(23)04549-X [pii]
AID - 10.1016/j.ijbiomac.2023.127651 [doi]
PST - ppublish
SO  - Int J Biol Macromol. 2024 Jan;254(Pt 3):127651. doi: 
      10.1016/j.ijbiomac.2023.127651. Epub 2023 Nov 8.