Multifunctional hybrid sulfonamides as novel therapeutic agents for Alzheimer's disease

Rayala Swetha; Devendra Kumar; Sukesh K. Gupta; Ankit Ganeshpurkar; Ravi Singh; Gopichand Gutti; Dileep Kumar; Srabanti Jana; Sairam Krishnamurthy; Sushil K. Singh

doi:10.4155/fmc-2019-0106

Multifunctional hybrid sulfonamides as novel therapeutic agents for Alzheimer's disease

Rayala Swetha
, Devendra Kumar
, Sukesh K. Gupta
, Ankit Ganeshpurkar
, Ravi Singh
, Gopichand Gutti
, Dileep Kumar
, Srabanti Jana
, Sairam Krishnamurthy
, Sushil K. Singh^*

^*Corresponding author for this work

Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal

Research output: Contribution to journal › Article › peer-review

43 Citations (Scopus)

Abstract

Aim: A breakthrough in modern medicine, in terms of treatment of Alzheimer's disease, is yet to be seen, as the scene is currently plagued with numerous clinical trial failures. Here, we are exploring multifunctional hybrid sulfonamides for their anti-Alzheimer activity due to the complex nature of the disease. Results & methodology: Compound 41 showed significant inhibition of MMP-2 (IC₅₀: 18.24 ± 1.62 nM), AChE (IC₅₀: 4.28 ± 0.15 μM) and BuChE (IC₅₀: 1.32 ± 0.02 μM). It also exhibited a metal-chelating property, as validated by an in vitro metal-induced Aβ aggregation assay using confocal fluorescence imaging. Whereas, MTT and DPPH assays revealed it to be nontoxic and neuroprotective with substantial antioxidant property. Conclusion: The present study puts forth potent yet nontoxic lead molecules, which foray into the field of multitargeted agents for the treatment of Alzheimer's disease.

Original language	English
Pages (from-to)	3161-3177
Number of pages	17
Journal	Future Medicinal Chemistry
Volume	11
Issue number	24
DOIs	https://doi.org/10.4155/fmc-2019-0106
Publication status	Published - 16-12-2019

All Science Journal Classification (ASJC) codes

Molecular Medicine
Pharmacology
Drug Discovery

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title = "Multifunctional hybrid sulfonamides as novel therapeutic agents for Alzheimer's disease",

abstract = "Aim: A breakthrough in modern medicine, in terms of treatment of Alzheimer's disease, is yet to be seen, as the scene is currently plagued with numerous clinical trial failures. Here, we are exploring multifunctional hybrid sulfonamides for their anti-Alzheimer activity due to the complex nature of the disease. Results \& methodology: Compound 41 showed significant inhibition of MMP-2 (IC50: 18.24 ± 1.62 nM), AChE (IC50: 4.28 ± 0.15 μM) and BuChE (IC50: 1.32 ± 0.02 μM). It also exhibited a metal-chelating property, as validated by an in vitro metal-induced Aβ aggregation assay using confocal fluorescence imaging. Whereas, MTT and DPPH assays revealed it to be nontoxic and neuroprotective with substantial antioxidant property. Conclusion: The present study puts forth potent yet nontoxic lead molecules, which foray into the field of multitargeted agents for the treatment of Alzheimer's disease.",

author = "Rayala Swetha and Devendra Kumar and Gupta, \{Sukesh K.\} and Ankit Ganeshpurkar and Ravi Singh and Gopichand Gutti and Dileep Kumar and Srabanti Jana and Sairam Krishnamurthy and Singh, \{Sushil K.\}",

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doi = "10.4155/fmc-2019-0106",

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T1 - Multifunctional hybrid sulfonamides as novel therapeutic agents for Alzheimer's disease

AU - Swetha, Rayala

AU - Kumar, Devendra

AU - Gupta, Sukesh K.

AU - Ganeshpurkar, Ankit

AU - Singh, Ravi

AU - Gutti, Gopichand

AU - Kumar, Dileep

AU - Jana, Srabanti

AU - Krishnamurthy, Sairam

AU - Singh, Sushil K.

PY - 2019/12/16

Y1 - 2019/12/16

N2 - Aim: A breakthrough in modern medicine, in terms of treatment of Alzheimer's disease, is yet to be seen, as the scene is currently plagued with numerous clinical trial failures. Here, we are exploring multifunctional hybrid sulfonamides for their anti-Alzheimer activity due to the complex nature of the disease. Results & methodology: Compound 41 showed significant inhibition of MMP-2 (IC50: 18.24 ± 1.62 nM), AChE (IC50: 4.28 ± 0.15 μM) and BuChE (IC50: 1.32 ± 0.02 μM). It also exhibited a metal-chelating property, as validated by an in vitro metal-induced Aβ aggregation assay using confocal fluorescence imaging. Whereas, MTT and DPPH assays revealed it to be nontoxic and neuroprotective with substantial antioxidant property. Conclusion: The present study puts forth potent yet nontoxic lead molecules, which foray into the field of multitargeted agents for the treatment of Alzheimer's disease.

AB - Aim: A breakthrough in modern medicine, in terms of treatment of Alzheimer's disease, is yet to be seen, as the scene is currently plagued with numerous clinical trial failures. Here, we are exploring multifunctional hybrid sulfonamides for their anti-Alzheimer activity due to the complex nature of the disease. Results & methodology: Compound 41 showed significant inhibition of MMP-2 (IC50: 18.24 ± 1.62 nM), AChE (IC50: 4.28 ± 0.15 μM) and BuChE (IC50: 1.32 ± 0.02 μM). It also exhibited a metal-chelating property, as validated by an in vitro metal-induced Aβ aggregation assay using confocal fluorescence imaging. Whereas, MTT and DPPH assays revealed it to be nontoxic and neuroprotective with substantial antioxidant property. Conclusion: The present study puts forth potent yet nontoxic lead molecules, which foray into the field of multitargeted agents for the treatment of Alzheimer's disease.

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Multifunctional hybrid sulfonamides as novel therapeutic agents for Alzheimer's disease

Abstract

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