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In silico identification of targets for a novel scaffold, 2-thiazolylimino-5-benzylidin-thiazolidin-4-one

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Abstract

Thiazolidinone derivatives have been found to exhibit a wide range of pharmacological activities. 2-Thiazolylimino-5-benzylidene-thiazolidin-4-one derivatives show antibacterial activity in in vitro tests which are comparable to marketed drugs. However, the target for this scaffold remains yet to be identified. In our work, we identified seven putative targets for this scaffold using web servers such as DRAR-CPI, PharmMapper, and TarFisDock and databases such as BindingDB and ChEMBL. Each of these servers used different algorithms and scoring functions for protein target identification. Further, these targets are substantiated by molecular docking analysis. Based on the docking studies, scaffold 2-thiazolylimino-5-benzylidene-thiazolidin-4-one is observed to exhibit affinity against diverse targets, particularly, towards COX-2, acetylcholinesterase, aldose reductase, and thyroid hormone receptor alpha. This study describes an initial probability that these proteins may be targeted by this scaffold.

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Author information

Authors and Affiliations

  1. Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, 160 062, Punjab, India

    Poornima Iyer, Jahnavi Bolla, Vivek Kumar & M. Elizabeth Sobhia

  2. Department of Pharmaceutical Technology – Process Chemistry, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Mohali, 160 062, Punjab, India

    Manjinder Singh Gill

Authors
  1. Poornima Iyer
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  2. Jahnavi Bolla
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  3. Vivek Kumar
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  4. Manjinder Singh Gill
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  5. M. Elizabeth Sobhia
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Corresponding author

Correspondence to M. Elizabeth Sobhia.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Fig. (S1). Slanted cladogram of the aligned protein sequences (TIFF 48 KB)

Fig. (S2). Top Hits from Specs Database Screening along with their Tanimoto Combo values* (TIFF 138 KB)

Fig. (S3). Superposition of ligand from 2FPT (gray) on the query green) (TIFF 1,376 KB)

11030_2015_9578_MOESM4_ESM.doc

Fig. (S4). Multiple sequence alignment of proteins 2H77, 3DCT, and 3K8S using ClustalX. The active-site residues are represented in box (doc 258 KB)

Fig. (S5). Thiazole Series of Compounds (doc 100 KB)

Fig. (S6). Benzothiazole Series of Compounds (doc 56 KB)

11030_2015_9578_MOESM7_ESM.doc

Fig. (S7). Structures of core moieties present in (a) Thiazole series and (b) Benzothiazole series of compounds (doc 320 KB)

Table S1. Targets from TarFisDock (doc 37 KB)

Table S2. Targets from DRAR-CPI (doc 37 KB)

Table S3. Targets from PharmMapper (doc 42 KB)

Table S4. Targets selected from different servers based on druggability (doc 40 KB)

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Iyer, P., Bolla, J., Kumar, V. et al. In silico identification of targets for a novel scaffold, 2-thiazolylimino-5-benzylidin-thiazolidin-4-one. Mol Divers 19, 855–870 (2015). https://doi.org/10.1007/s11030-015-9578-2

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