title: Synthesis, molecular properties, toxicity and biological evaluation of some new substituted imidazolidine derivatives in search of potent anti-inflammatory agents.
abstract: The aim of this study was to design and synthesize pharmaceutical agents containing imidazolidine heterocyclic ring in the hope of developing potent, safe and orally active anti-inflammatory agents. A number of substituted-imidazolidine derivatives (3a-k) were synthesized starting from ethylene diamine and aromatic aldehydes. The imidazolidine derivatives (3a-k) were investigated for their anticipated anti-inflammatory, and analgesic activity in Wistar albino rats and Swiss albino mice, respectively. Bioactivity score, molecular and pharmacokinetic properties of the imidazolidine derivatives were calculated by online computer software programs viz. Molinspiration and Osiris property explorer. The results of biological testing indicated that among the synthesized compounds only three imidazolidine derivatives namely 4-[1,3-Bis(2,6-dichlorobenzyl)-2-imidazolidinyl]phenyl-diethylamine (3g), 4-[1,3-Bis(3-hydroxy-4-methoxybenzyl)-2-imidazolidinyl]phenyl-diethylamine (3i) and 4-(1,3-Bis(4-methoxybenzyl)-4-methylimidazolidin-2-yl)-phenyl-diethylamine (3j) possess promising anti-inflammatory and analgesic actions. Additionally these derivatives displayed superior GI safety profile (low severity index) with respect to the positive control, Indomethacin. All synthesized compounds showed promising bioactivity score for drug targets by Molinspiration software. Almost all the compounds were predicted to have very low toxicity risk by Osiris online software. Compound number (3i) emerged as a potential candidate for further research as it obeyed Lipinski's rule of five for drug likeness, exhibited promising biological activity in-vivo and showed no risk of toxicity in computer aided screening.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi 110062, India.
authors.forename: Asif
authors.initials: A
authors.lastname: Husain
authors.affiliation: Health Information Technology Department, Jeddah Community College, King Abdulaziz University, P.O. Box-80283, Jeddah 21589, Saudi Arabia.
authors.forename: Aftab
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Pharmacy, Oman Medical College, Muscat, Oman.
authors.forename: Shah Alam
authors.initials: SA
authors.lastname: Khan
authors.affiliation: Department of Pharmacy, Guru Ram Das Institute of Management and Technology, Dehradun 248009, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Asif
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi 110062, India.
authors.forename: Rubina
authors.initials: R
authors.lastname: Bhutani
authors.affiliation: Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors.forename: Fahad A
authors.initials: FA
authors.lastname: Al-Abbasi
keywords: Analgesic; Anti-inflammatory; Imidazolidine; Indomethacin