2,4-dihydroxy benzaldehyde derived Schiff bases as small molecule Hsp90 inhibitors: Rational identification of a new anticancer lead

Gupta, Sayan Dutta; Revathi, B.; Mazaira, Gisela Ileana; Galigniana, Mario D.; Subrahmanyam, C. V. S.; Gowrishankar, N. L.; Raghavendra, Narasimha

doi:10.1016/j.bioorg.2015.02.003

Cited by 35 publications

(10 citation statements)

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“…1 H NMR spectra show the characteristic signals of the different systems present in these Schiff bases [ 34 , 35 , 36 ]. At a low field, the signals corresponding to the protons of the imidazole and the -OH present in the salicylidene ring were observed.…”

Section: Resultsmentioning

confidence: 99%

“…Some potential targets that may be targeted by benzimidazole compounds can be involved in the underlying mechanism for this behavior, including the inhibition of Aurora A kinase, cyclin-dependent kinase (CDK), and dihydrofolate reductase [ 29 ]; however, the inhibition of heat shock proteins (Hsps) represents the most promising proposed mechanism for the future development of anticancer agents using the generated Schiff bases in the present study. L4 is known to be a potent and selective inhibitor of the molecular chaperone Hsp90, with important cytotoxic consequences versus carcinoma cells (PC-3) [ 36 ]. Additionally, the molecular docking studies discussed below indicated that the ligands could interact with molecular targets through hydrophilic bonds and conventional hydrogen bonds, in addition to pi-alkyl interactions with the three aromatic rings, which may also be the mechanisms involved in the inhibition of human DNA topoisomerase I [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

“…With benzimidazoles prepared, we proceeded to carry out the synthesis of Schiff bases from salicylaldehyde and 2,4-dihydroxybenzaldehyde (from Sigma-Aldrich) by nucleophilic addition to obtain the corresponding imines in methanol or ethanol as suggested by the literature [ 32 , 36 , 67 ].…”

Section: Methodsmentioning

confidence: 99%

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In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes

et al. 2021

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Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1H-benzimidazol-2-yl)aniline, salicylaldehyde, and 2,4-dihydroxybenzaldehyde were synthesized and characterized using different spectroscopic methods. Besides their cytotoxic activities, they were examined in human U-937 cells, primate kidney non-cancerous COS-7, and six other, different human tumor cell lines: U251, PC-3, K562, HCT-15, MCF-7, and SK-LU-1. In addition, the synthesized compounds were screened for in vitro antiparasitic activity against Leishmania braziliensis, Plasmodium falciparum, and Trypanosoma cruzi. Additionally, antibacterial activities were examined against two Gram-positive strains (S. aureus ATCC® 25923, L. monocytogenes ATCC® 19115) and two Gram-negative strains (E. coli ATCC® 25922, P. aeruginosa ATCC® 27583) using the microdilution method. The lanthanide complexes generally exhibited increased biological activity compared with the free Schiff base ligands. Interactions between the tested compounds and model membranes were examined using differential scanning calorimetry (DSC), and interactions with calf thymus DNA (CT-DNA) were investigated by ultraviolet (UV) absorption. Molecular docking studies were performed using leishmanin (1LML), cruzain (4PI3), P. falciparum alpha-tubulin (GenBank sequence CAA34101 [453 aa]), and S.aureus penicillin-binding protein 2a (PBP2A; 5M18) as the protein receptors. The results lead to the conclusion that the synthesized compounds exhibited a notable effect on model membranes imitating mammalian and bacterial membranes and rolled along DNA strands through groove interactions. Interactions between the compounds and studied receptors depended primarily on ligand structures in the molecular docking study.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes

et al. 2021

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“…Benzaldehyde, which is known to have very effective cytotoxic potential, is major volatile compounds found in the strain BPS_CRB14. This compound was accounted by Ulker et al, 2013, Gupta et al, 2015, who stated that benzaldehyde has the capacity to destroy cancer cells at a minimum concentration. Moreover, Ergotaman-3′, 6′, 18-Trione, 9, 10-Dihydro-12′-Hydroxy-2′-Methyl-5′-(Phenyl Methyl) (5′-α, 10-α) was found in isolate BPS_CRB14, that have antimicrobial potential reported by Shanthakumar and Kumar (2015), who stated that the compounds Ergotaman-3′, 6′, 18-Trione, 9, 10-Dihydro-12′-Hydroxy-2′-Methyl-5′-(Phenyl Methyl) (5′-α, 10-α) exhibited antimicrobial activity against several tested pathogens: S. enteric , S. flexneri , E. coli and K. pneumoniae, respectively.…”

Section: Resultsmentioning

confidence: 99%

Phylogenetic affiliation and determination of bioactive compounds of bacterial population associated with organs of mud crab, Scylla olivacea

Zote

Passari

Zothanpuia

et al. 2018

Saudi Journal of Biological Sciences

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Mud crab belongs to the genus Scylla is an economically valuable and preferred species for costal aquaculture in Asian countries, including India. In recent years, there has been a tremendous expansion of Scylla farming, which has led to increasing research on its habit and habitats. However, there has been no study undertaken to understand the role of the bacterial population associated with the different organs of the mud crab, Scylla olivacea. In total, 43 isolates were recovered from four selected parts of the crab (carapace, n = 18; abdomen n = 11; leg, n = 8; and hand, n = 6), and the 16S rRNA gene was used to identify the bacterial isolates. The antimicrobial potential along with the detection of modular polyketide synthase (PKSI), cytochrome P450 hydroxylase (CYP) and non-ribosomal peptide synthetase (NRPS) gene clusters were investigated to show a relationship among the biosynthetic genes with their useful aspects. Additionally, the potential three strains (BPS_CRB12, BPS_CRB14 and BPS_CRB41), which showed significant antimicrobial activities, also showed the presence of twenty volatile compounds (VOCs) using GC–MS analysis. We conclude that the strain Aneurinibacillus aneurinilyticus BPS_CRB41 could be source for the production of bioactive compounds.

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“…In continuation of our quest toward the discovery of small‐molecule inhibitors of Hsp90, in this article, we report the molecular modeling, chemical synthesis, and biological evaluation of N ‐pyridoyl‐Δ 2 ‐pyrazolines as Hsp90 inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Discovery of N‐pyridoyl‐Δ²‐pyrazolines as Hsp90 inhibitors

Kadasi

Yerroju

Gaddam

et al. 2019

Archiv der Pharmazie

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Hsp90, as a key molecular chaperone, plays an important role in modulating the activity of many cell signaling proteins and is an attractive target for anticancer therapeutics.Herein, we report the discovery of N-pyridoyl-Δ 2 -pyrazoline analogs as novel Hsp90 inhibitors by integrated approaches of drug design, organic synthesis, cell biology, and qualitative proteomic analysis. Novel chemical compounds were designed and optimized in the adenosine triphosphate-binding site of Hsp90; lead optimized compounds were found to have significant interactions with Asp93 and other amino acids crucial for Hsp90 inhibition. The designed compounds were synthesized by a two-step procedure; different aromatic aldehydes were reacted with various acetophenones to form substituted 1,3-diphenyl-prop-2-enones (Ic-Io), which upon reaction with isonicotinic acid hydrazide in the presence of glacial acetic acid form N-pyridoyl-Δ 2 -pyrazoline compounds (PY1-PY13). Compounds PY3, PY2, and PY1 were identified as potential leads amongst the series, with promising anticancer activity against human breast cancer and melanoma cells, and the ability to inhibit Hsp90 similar to radicicol by drug-affinity responsive target stability proteomic analysis in a whole-cell assay.

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2,4-dihydroxy benzaldehyde derived Schiff bases as small molecule Hsp90 inhibitors: Rational identification of a new anticancer lead

Cited by 35 publications

References 41 publications

In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes

In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes

Phylogenetic affiliation and determination of bioactive compounds of bacterial population associated with organs of mud crab, Scylla olivacea

Discovery of N‐pyridoyl‐Δ²‐pyrazolines as Hsp90 inhibitors

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2,4-dihydroxy benzaldehyde derived Schiff bases as small molecule Hsp90 inhibitors: Rational identification of a new anticancer lead

Cited by 35 publications

References 41 publications

In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes

In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes

Phylogenetic affiliation and determination of bioactive compounds of bacterial population associated with organs of mud crab, Scylla olivacea

Discovery of N‐pyridoyl‐Δ2‐pyrazolines as Hsp90 inhibitors

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Discovery of N‐pyridoyl‐Δ²‐pyrazolines as Hsp90 inhibitors