Molecular Docking Studies of Novel Furan-Azetidinone Hybrid Compounds as Potential Antifungal Agents

Abstract

Antifungal resistance poses a significant clinical challenge for treating invasive fungal infections. Candida albicans is responsible for candidiasis including invasive fungal infections, where most patients are immunocompromised. Therefore the success of treatment depends significantly on the effectiveness of the antifungal agent. In this study, sixteen novel furan derivatives containing the azetidinone moiety were designed and synthesized to arrive at potentially effective antifungal agents. In silico antifungal activity was carried out to identify the specificity of the novel furan derivatives for the fungal proteins using 'Glide'. Molecular docking studies were conducted on two antifungal targets; Dihydrofolate reductase of C.albicans (PDB ID: 4HOE); N-myristoyl transferase of C.albicans (PDB ID: 1IYK). Molecular docking was carried out at the Standard Precision (SP) and Extra Precision (XP) mode. The docked poses were ranked according to their docking scores (GScore) and their binding energy with the enzyme. The results obtained for the docking of the title compounds with N-myristoyl transferase of C.albicans is quite promising. Molecular docking suggests that compounds 4d, 4e, and 4h are potential inhibitors of N-myristoyl transferase and are specific in binding at the active site of the enzyme. They form Hbond with THR 211 and pi-pi stacking interactions with PHE 117, TRY 354, and TRY 225 at the active site of the protein, similar to the standard drug. However the test compounds show low docking scores against Dihydrofolate reductase of C.albicans indicating that they may not be effective against it.

Studi Interaksi Senyawa Turunan Saponin dari Daun Bidara Arab (Ziziphus spina-christi L.) sebagai Antiseptik Alami secara In Silico

“…Makromolekul target yang digunakan dalam penelitian ini merupakan reseptor pada beberapa bakteri yang meliputi Penicillin-Binding Protein 3 (PBP3) dari Escherichia coli [9], Filamentous Temperature-Sensitive Mutant Z (FtsZ) dari Staphylococcus epidermidis [10], dan N-myristoyl Transferase dari Candida albicans [11]…”

Studi Interaksi Senyawa Turunan Saponin dari Daun Bidara Arab (Ziziphus spina-christi L.) sebagai Antiseptik Alami secara In Silico

“…Makromolekul target yang digunakan dalam penelitian ini merupakan reseptor pada beberapa bakteri yang meliputi Penicillin-Binding Protein 3 (PBP3) dari Escherichia coli [9], Filamentous Temperature-Sensitive Mutant Z (FtsZ) dari Staphylococcus epidermidis [10], dan N-myristoyl Transferase dari Candida albicans [11]. Makromolekul target tersebut diperoleh dari web Protein Data Bank (http://www.rcsb.org/pdb) dengan kode PDB masing-masing 4EBN dengan resolusi 2,85 Å [13]…”

“…Daun bidara arab ini telah banyak digunakan sebagai cairan antiseptik alami dalam pencegahan infeksi pada permukaan kulit. Melalui penelitian ini akan diprediksikan lebih lanjut mengenai afinitas dan interaksi molekular yang terbentuk antara senyawa christinin-A, B, C, dan D terhadap reseptor target pada beberapa bakteri yang meliputi Penicillin-Binding Protein 3 (PBP3) dari Escherichia coli [9], Filamentous Temperature-Sensitive Mutant Z (FtsZ) dari Staphylococcus epidermidis [10], dan N-myristoyl Transferase dari Candida albicans [11].…”

“…Dalam upaya pengembangan antiseptik alami dari daun bidara arab, maka dilakukan uji aktivitas antara beberapa senyawa turunan glikosida saponin triterpenoidal, yaitu christinin-A, B, C, dan D terhadap reseptor target pada beberapa bakteri yang meliputi Penicillin-Binding Protein 3 (PBP3) dari Escherichia coli [9], Filamentous Temperature-Sensitive Mutant Z (FtsZ) dari Staphylococcus epidermidis [10], dan N-myristoyl Transferase dari Candida albicans [11]. Penelitian ini dilakukan dengan memanfaatkan studi in silico yang bertujuan untuk mengidentifikasi, mengevaluasi, dan mengekplorasi interaksi molekular yang terbentuk sehingga diharapkan didapat senyawa turunan glikosida saponin triterpenoidal yang paling berpotensi sebagai antiseptik alami.…”

Facile synthesis of two azete-steroid derivatives and theoretical evaluation of its interaction with the aromatase enzyme

“…Analyzing the hypothesis mentioned above and some reports which suggest that the formation of binary complexes between some compounds that act as ligands with several target biomolecules could induce changes in many activities of some biological systems [48][49][50][51][52][53]; Therefore, in this study, was carried out a theoretical analysis on the interaction of both compound 9 or 10 with Dwd3 protein using exemestane and anastrozole (aromatase inhibitors) [54] as a control in a Doc- kingServer [23]; here, it is important to mention that Dockingserver was used because we believe that it is one of the most complete to analyze the protein-drug interaction.…”