Polysubstituted 2-aminoimidazoles as anti-biofilm and antiproliferative agents: Discovery of potent lead

Most of the human bacterial infections are associated with the biofilm formation and the natural tolerance of biofilms to antibiotics challenges treatment. Because of their low immunity, cancer patients are especially susceptible to bacterial infections. Compounds with anti-biofilm activity could therefore become a useful adjunct to chemotherapy, in particular if they also show antiproliferative activities. Taking this into consideration and as a result of our continuous interest in 2-aminoimidazole derivatives, we have designed and synthesized a series of novel polysubstituted 2-aminoimidazoles (20a-x). The compounds were evaluated against a panel of three bacterial strains for their biofilm and planktonic growth inhibitory activity and most of them show promising results. Furthermore, the synthesized compounds were evaluated against various cancer cell lines and almost all the compounds were found to possess potent antiproliferative activity. The substitution pattern at the C-4 position and the aryl carboxamide ring at the N-1 position have major effects on the biofilm inhibitory and antiproliferative activity. Especially, the introduction of a p-methyl group at the carboxamide ring remarkably enhances both the anti-biofilm and antiproliferative activity. The two most potent compounds (20i & 20r) were further studied for their antiproliferative activity and a flow cytometer-based cell cycle experiment was performed, which revealed their capability to induce G2/M phase cell cycle arrest. Based on these results, these two new compounds having potential to target both cancer proliferation and microbial biofilms might be used in single drug monotherapy. © 2017 Elsevier Masson SAS

Gill R.K.1, 2 , Kumar V.3 , Robijns S.C.A.4 , Steenackers H.P.L.4 , Van Der Eycken E.V. , Bariwal J.1, 7
Elsevier Masson SAS
  • 1 Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab 142001, India
  • 2 Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143 005, India
  • 3 Department of Pharmaceutical Sciences, University of Nebraska Medical Centre, Omaha, NE 68198, United States
  • 4 Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20, Leuven, 3001, Belgium
  • 5 Laboratory for Organic and Microwave-Assisted Chemistry (LOMAC), University of Leuven (KU Leuven), Celestijnenlaan 200F, Leuven, 3001, Belgium
  • 6 Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya street, Moscow, 117198, Russian Federation
  • 7 Shiva Institute of B. Pharmacy, Chandpur, Bilaspur, Himachal Pradesh 174004, India
Ключевые слова
2-aminoimidazoles; Anti-biofilm; Antiproliferative
Дата создания
Дата изменения
Постоянная ссылка

Другие записи

Metin A.D., Pelinovsky E., Yalciner A.C., Zaytsev A., Tarakcioglu G.O., Yalciner B., Kurkin A.
13th International MEDCOAST Congress on Coastal and Marine Sciences, Engineering, Management and Conservation, MEDCOAST 2017. Mediterranean Coastal Foundation. Том 2. 2017. С. 1143-1154