Details

Autor(en) / Beteiligte

• Kumara, H.K.
• Suhas, R.
• Suyoga Vardhan, D.M.
• Shobha, M.
• Channe Gowda, D.

Titel

Imidazolo and tryptophan-imidazolo hybrid derived ureas/thioureas as potent bioactive agents – SAR and molecular modelling studies

Ist Teil von

• Bioorganic chemistry, 2019-05, Vol.86, p.34-38

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] •Syntheses of urea/thiourea derivatives of imidazolo and tryptophan-imidazolo hybrid.•Antioxidant, anti-inflammatory and antimicrobial activities were carried out.•Molecular modelling studies were carried out and correlated with biological results.•Correlation showed that EDGs & EWGs help in antioxidant & antimicrobial and anti-inflammatory activities respectively. Herein, we used an imidazole derivative (IMD) which showed promising antibacterial, antifungal and antioxidant properties in our earlier investigation. Prompted by this, we converted IMD to hydrazide (IMH) by hydrazinolysis which was derivatized to various ureas (3–7) and thioureas (8–12). On the other hand, IMH was conjugated to Boc-Trp-OH as it has been shown in the past that hybridization of two molecules produced promising biologically active compounds. Boc of the conjugate was removed and further converted into several urea (14–18) and thiourea (19–23) derivatives. All the title compounds so also the starting materials and intermediates were assessed for potential biological applications. The results showed that compounds 3, 4, 8, 9, 14, 15, 19 and 20 were excellent antioxidants as revealed by DPPH, DMPD and ABTS assays. Further, certain analogues like 5–7, 10–12, 16–18 and 21–23 were found to be potent antimicrobials against pathogenic bacteria and fungi whereas good anti-inflammatory activity was obtained for molecules 5–7, 10–12, 16–18 and 21–23. All together, derivatives of the conjugates have shown superior activity over non-conjugated compounds and the former have exhibited potent activity against standard drugs in all the assays. In a quest to understand the binding interactions of the compounds with active site of tyrosine kinase (PDB ID: 2HCK), glucosamine-6-phosphate (GlcN-6-P) synthase (PDB ID: 2VF5) and cyclooxygenase-2 (PDB ID: 1CX2) enzymes, the correlation studies were conducted using molecular modelling which showed good receptor binding interactions with several amino acids of the enzymes. Overall, the current investigation may be considered for the discovery of lead compound(s) for treating multiple disorder conditions using singular molecular entity.