Abstract:
:A new series of pyrazolo[3,4-d]pyridazin-7-one derivatives were synthesised and evaluated for their in vitro antileishmanial activity against Leishmania amazonensis promastigote and axenic amastigote forms. The results showed that the pyrazolo[3,4-d]-pyridazin-7-one-N-acylhydrazone-(bi)thiophene hybrids 5b, 6b and 6d exhibit better antileishmanial activity with IC50 84.96, 3.63 and 10.79 μM, against the promastigote form and IC50 32.71, 2.32 and >100 μM against the axenic amastigote form, respectively. The active compounds had their cytotoxicity tested against macrophages and fibroblast cells with a higher selectivity index than 10 for compounds 6b and 6d. Molecular docking studies were performed for all active compounds using the enzyme trypanothione reductase (TR) to investigate a possible action mechanism. The results suggested that active compounds had interactions with the residues of amino acids Gly 13, Thr 51, Thr 160, Gly 161, Tyr 198, Arg 287, Asp 327, Thr 335, which may inhibit the enzyme TR.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Jacomini AP,Silva MJV,Silva RGM,Gonçalves DS,Volpato H,Basso EA,Paula FR,Nakamura CV,Sarragiotto MH,Rosa FAdoi
10.1016/j.ejmech.2016.08.048subject
Has Abstractpub_date
2016-11-29 00:00:00pages
340-349eissn
0223-5234issn
1768-3254pii
S0223-5234(16)30701-2journal_volume
124pub_type
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