Synthesis, anti-bacterial and anti-protozoal activities of amidinobenzimidazole derivatives and their interactions with DNA and RNA

Journal of Enzyme Inhibition and Medicinal Chemistry
Andrea BistrovićSilvana Raić-Malić

Abstract

Amidinobenzimidazole derivatives connected to 1-aryl-substituted 1,2,3-triazole through phenoxymethylene linkers 7a-7e, 8a-8e, and 9a-9e were designed and synthesised with the aim of evaluating their anti-bacterial and anti-trypanosomal activities and DNA/RNA binding affinity. Results from anti-bacterial evaluations of antibiotic-resistant pathogenic bacteria revealed that both o-chlorophenyl-1,2,3-triazole and N-isopropylamidine moieties in 8c led to strong inhibitory activity against resistant Gram-positive bacteria, particularly the MRSA strain. Furthermore, the non-substituted amidine and phenyl ring in 7a induced a marked anti-bacterial effect, with potency against ESBL-producing Gram-negative E. coli better than those of the antibiotics ceftazidime and ciprofloxacin. UV-Vis and CD spectroscopy, as well as thermal denaturation assays, indicated that compounds 7a and 8c showed also binding affinities towards ctDNA. Anti-trypanosomal evaluations showed that the p-methoxyphenyl-1,2,3-triazole moiety in 7b and 9b enhanced inhibitory activity against T. brucei, with 8b being more potent than nifurtimox, and having minimal toxicity towards mammalian cells.

References

May 15, 2002·European Journal of Medicinal Chemistry·Vera KlimesováJarmila Kaustová
May 17, 2002·The Journal of Antibiotics·Marijana HranjecGrace Karminski-Zamola
Sep 6, 2002·Journal of Medicinal Chemistry·Thomas C KühlerJan-Erik Sjöström
Mar 18, 2004·Oligonucleotides·Jean-Louis Mergny, Laurent Lacroix
Aug 24, 2004·Combinatorial Chemistry & High Throughput Screening·R W DeSimoneD A Pippin
Jun 24, 2005·The Journal of Antimicrobial Chemotherapy·A J SmithC G Gemmell
Aug 16, 2005·Bioorganic & Medicinal Chemistry·Mohamed A IsmailDavid W Boykin
Oct 27, 2007·Journal of Medicinal Chemistry·Nahoum G AnthonyRoger D Waigh
Mar 5, 2008·European Journal of Medicinal Chemistry·K F Ansari, C Lal
Mar 26, 2008·Chemical Reviews·Jason R Thomas, Paul J Hergenrother
Aug 12, 2008·Current Medicinal Chemistry·Santanu Bhattacharya, Padmaparna Chaudhuri
Jan 20, 2009·European Journal of Medicinal Chemistry·Ganesh Rajaram JadhavCharansingh Harnamsingh Gill
Jun 2, 2009·Bioorganic & Medicinal Chemistry Letters·Laixing HuNorman Abood
Nov 26, 2009·Journal of Medicinal Chemistry·Stanislav A BakunovRichard R Tidwell
Mar 24, 2010·Chemical Society Reviews·C Oliver Kappe, Erik Van der Eycken
Oct 16, 2010·Organic & Biomolecular Chemistry·Padraic S NagleIsabel Rozas
Dec 22, 2011·ACS Chemical Biology·Lirui Guan, Matthew D Disney
Jul 31, 2012·European Journal of Medicinal Chemistry·Moloy BanerjeeDavid W Boykin
Aug 7, 2012·Macromolecular Bioscience·Katherine A GibneyKenichi Kuroda
Feb 9, 2013·RNA Biology·Yadong ZhengJanette E Bradley
Dec 3, 2013·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·G LuoA S Ibrahim
Dec 5, 2013·The FEBS Journal·Mohammed A HusainMohammad Tabish
Mar 8, 2014·European Journal of Medicinal Chemistry·Monika GabaChander Mohan
Aug 5, 2014·European Journal of Medicinal Chemistry·Dmytro HavrylyukRoman Lesyk
Nov 5, 2014·Frontiers in Microbiology·Nadim CassirPhilippe Brouqui
Dec 7, 2014·European Journal of Medicinal Chemistry·Geeta Yadav, Swastika Ganguly
Jan 22, 2015·Antimicrobial Agents and Chemotherapy·Christopher A RiceDennis E Kyle
May 9, 2015·Archives of Biochemistry and Biophysics·Sayeed Ur RehmanMohammad Tabish
Aug 22, 2015·Journal of Applied Microbiology·W PanC Liu
Nov 19, 2015·Bioorganic & Medicinal Chemistry·Silvija MaračićSilvana Raić-Malić

❮ Previous
Next ❯

Citations

Apr 16, 2020·International Journal of Molecular Sciences·Vishma Pratap SurAmitava Moulick
Aug 31, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Livio RacanéSilvana Raić-Malić

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
column chromatography

Software Mentioned

Origin
GraphPad Prism

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

African Trypanosomiasis

African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.