Mahesh Pattabiraman | University of Nebraska at Kearney (original) (raw)
Papers by Mahesh Pattabiraman
Advanced structured materials, 2024
The FASEB Journal, May 1, 2022
Pharmacological Research, Mar 1, 2021
All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacol... more All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacologists to generate new therapeutics for chronic pain. The vanilloid phytochemicals, which include curcumin, capsaicin, and gingerol, have been shown to alleviate pain. However, there is little to no literature on the interaction of vanilloid phytochemicals with ARs. In this study, photochemical methods were used to generate a novel isomer of curcumin (cis-trans curcumin or CTCUR), and the interactions of both curcumin and CTCUR with the two Gs-linked AR subtypes were studied. Competitive binding assays, docking analysis, and confocal fluorescence microscopy were performed to measure binding affinity; cell survival assays were used to measure toxicity; and cAMP assays were performed to measure receptor activation. Competitive binding results indicated that CTCUR binds to both AR A2A and AR A2B with Ki values of 5 µM and 7 µM, respectively, which is consistent with our docking results. Fluorescence microscopy data also shows binding for A2B and A2A. Cell survival results show that CTCUR and CUR are nontoxic at the tested concentrations in these cell lines. Overall, our results suggest that vanilloid phytochemicals may be slightly modified to increase interaction with Gs-ARs, and thereby can be further explored to provide a novel class of non-opioid antinociceptives.
The FASEB Journal, May 1, 2022
Pharmaceuticals
Adenosine receptors (ARs) are being explored to generate non-opioid pain therapeutics. Vanilloid ... more Adenosine receptors (ARs) are being explored to generate non-opioid pain therapeutics. Vanilloid compounds, curcumin, capsaicin, and vanillin possess antinociceptive properties through their interactions with the transient receptor potential channel family. However, their binding with adenosine receptors has not been well studied. The hypothesis in this study was that a vanilloid compound, cis-trans curcumin (CTCUR), binds to each of the two Gi-linked AR subtypes (A1AR and A3AR). CTCUR was synthesized from curcumin (CUR) using the cavitand-mediated photoisomerization technique. The cell lines transfected with the specific receptor (A1AR or A3AR) were treated with CTCUR or CUR and the binding was analyzed using competitive assays, confocal microscopy, and docking. The binding assays and molecular docking indicated that CTCUR had Ki values of 306 nM (A1AR) and 400 nM (A3AR). These values suggest that CTCUR is selective for Gi-linked ARs (A1AR or A3AR) over Gs-linked ARs (A2AAR or A2BA...
Journal of Molecular Structure
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
1. SCIENTIFIC SUMMARY The third year of research supported by ACS-PRF resulted in exploration of ... more 1. SCIENTIFIC SUMMARY The third year of research supported by ACS-PRF resulted in exploration of two different groups of alkenes for homoand heterodimerization: (a) extended and cross conjugated diene systems (dibenzylidene acetones), and unsymmetrical chalcones (phenyl styryl ketones). These new class of photosubstrates were explored to understand the excited-state photocycloaddition (PCA) characteristics of the alkenes. In both cases native efficiency of PCA is significantly lower in solution phase and solid state, and several PCA products are possible. Complexing the photoreactants to γ-cyclodextrin (γ-CD) increases PCA efficiency resulting formation of a single product. Investigation of the photochemical and photophysical features of the host-guest complex, evaluation of its association constants experimentally, and computational analysis of the complex structures provided insight into the nature of weak interactions involving aromatic groups and excited state reactivity of such...
![Research paper thumbnail of Supramolecular assistance of [2+2] photocycloaddition for cross-photodimerization](https://attachments.academia-assets.com/120874213/thumbnails/1.jpg)
](Photocycloaddition (PCA) of alkenes is an important reaction as it is used in several areas of fu... more Photocycloaddition (PCA) of alkenes is an important reaction as it is used in several areas of fundamental and applied research. Due to its significance, there are numerous articles and reviews in chemical literature that document various aspect of this reaction -such as application in synthesis, photopolymerization, materials research, etc. Despite its importance, the vast majority of the reports are focused on the reaction between identical alkenes (homo-dimerization), while PCA between non-identical alkenes (cross-dimerization) has been grossly under-explored. In this review we have complied the reports on cross-dimerization reactions affected through supramolecular methods, which can be broadly classified based on two broad approaches: (a) crystal-engineering or (b) templation in solution or slurry. Both methods are based on the utilization of favorable intermolecular interaction between non-identical alkenes, and the use of a templating agent that promotes heteroalkene arrangement in the ground state, which, upon photoexcitation yield the cross-dimer selectively.
Pharmacological Research, 2021
All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacol... more All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacologists to generate new therapeutics for chronic pain. The vanilloid phytochemicals, which include curcumin, capsaicin, and gingerol, have been shown to alleviate pain. However, there is little to no literature on the interaction of vanilloid phytochemicals with ARs. In this study, photochemical methods were used to generate a novel isomer of curcumin (cis-trans curcumin or CTCUR), and the interactions of both curcumin and CTCUR with the two Gs-linked AR subtypes were studied. Competitive binding assays, docking analysis, and confocal fluorescence microscopy were performed to measure binding affinity; cell survival assays were used to measure toxicity; and cAMP assays were performed to measure receptor activation. Competitive binding results indicated that CTCUR binds to both AR A2A and AR A2B with Ki values of 5 µM and 7 µM, respectively, which is consistent with our docking results. Fluorescence microscopy data also shows binding for A2B and A2A. Cell survival results show that CTCUR and CUR are nontoxic at the tested concentrations in these cell lines. Overall, our results suggest that vanilloid phytochemicals may be slightly modified to increase interaction with Gs-ARs, and thereby can be further explored to provide a novel class of non-opioid antinociceptives.
Journal of the American Chemical Society, 1993
Regioselectivity and stereoselectivity in organic photochemistry continue to be topics of great i... more Regioselectivity and stereoselectivity in organic photochemistry continue to be topics of great interest. In recent years, such selectivity has been achieved to a considerable extent in photochemical processes carried out in constrained media.1" Of particular interest are the remarkable results obtained in zeolites. Zeolites have recently been shown to exert a significant influence on the unimolecular photoreactivity of included guest molecules, as in Norrish Type I and Type I1 photoreactions.7 In the area of bimolecular photoprocesses, zeolites have been shown to influence the course of [2 + 21 photodimerization of acenaphthylene,* but no such studies have been reported for [2 + 21 photocycloaddition reactions of enones, a reaction of recognized mechanistic importan~e.~ In an initial foray in this area, the effects of zeolites on photodimerizations of cyclopentenone (1) and cyclohexenone (2) have been investigated. Little control over the regiochemistry of such reactions is attainable when they are carried out in isotropic solvents.lOJ1 In this report, we show that a relatively high degree of regioselectivity in enone photodimerization can be achieved in zeolites, due to size constriction effects in the supercages of X-and Y-type faujasites as well as the complexing ability of the charge-compensating cation of the zeolite on included guests. (1) Photochemistry in micelles: (a) Thomas,
Journal of Photochemistry and Photobiology A: Chemistry, 2021
The supramolecular photocycloaddition (PCA) of 3-(phenyl)acrylic acid has been extensively pursue... more The supramolecular photocycloaddition (PCA) of 3-(phenyl)acrylic acid has been extensively pursued by chemists to study weak interactions and synthesize substituted cyclobutanes. The stereo- and regioselectivity of the products in a supramolecularly affected reaction are often used as a probe for assessing the nature of weak interactions and/or molecular ambience of the reactants. However, some crucial aspects of this chemistry have often remained underexplored in the past, especially within the context of interpreting strength and directionality of interactions based on reaction outcomes. We present a detailed study of the cavitand-mediated PCA of a new and suitable reactant (3-(naphthyl)acrylic acids) that exhibits labile photo-reversible chemistry, which is suitable for exploring previously un-explored aspects of the supramolecular PCA chemistry. Our studies afford important insights about this chemistry that should be considered while using product selectivity as a proxy for deducing intermolecular interactions.
Molecules
Singlet oxygen (1O2) is the excited state electronic isomer and a reactive form of molecular oxyg... more Singlet oxygen (1O2) is the excited state electronic isomer and a reactive form of molecular oxygen, which is most efficiently produced through the photosensitized excitation of ambient triplet oxygen. Photochemical singlet oxygen generation (SOG) has received tremendous attention historically, both for its practical application as well as for the fundamental aspects of its reactivity. Applications of singlet oxygen in medicine, wastewater treatment, microbial disinfection, and synthetic chemistry are the direct results of active past research into this reaction. Such advancements were achieved through design factors focused predominantly on the photosensitizer (PS), whose photoactivity is relegated to self-regulated structure and energetics in ground and excited states. However, the relatively new supramolecular approach of dictating molecular structure through non-bonding interactions has allowed photochemists to render otherwise inactive or less effective PSs as efficient 1O2 gen...
Nutrients
Fulminant hepatic failure (FHF) is a rare, life-threatening liver disease with a poor prognosis. ... more Fulminant hepatic failure (FHF) is a rare, life-threatening liver disease with a poor prognosis. Administration of D-galactosamine (GalN) and lipopolysaccharide (LPS) triggers acute liver injury in mice, simulating many clinical features of FHF in humans; therefore, this disease model is often used to investigate potential therapeutic interventions to treat FHF. Recently, suppression of the nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome, was shown to alleviate the severity of GalN/LPS-induced liver damage in mice. Therefore, the goal of this study was to find dietary exosome-like nanoparticles (ELNs) with therapeutic potential in curbing FHF by suppressing the NLRP3 inflammasome. Seven commonly consumed mushrooms were used to extract ELNs. These mushrooms were found to contain ELNs composed of RNAs, proteins, and lipids. Among these mushroom-derived ELNs, only shiitake mushroom-derived ELNs (S-ELNs) substantiall...
Advanced structured materials, 2024
The FASEB Journal, May 1, 2022
Pharmacological Research, Mar 1, 2021
All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacol... more All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacologists to generate new therapeutics for chronic pain. The vanilloid phytochemicals, which include curcumin, capsaicin, and gingerol, have been shown to alleviate pain. However, there is little to no literature on the interaction of vanilloid phytochemicals with ARs. In this study, photochemical methods were used to generate a novel isomer of curcumin (cis-trans curcumin or CTCUR), and the interactions of both curcumin and CTCUR with the two Gs-linked AR subtypes were studied. Competitive binding assays, docking analysis, and confocal fluorescence microscopy were performed to measure binding affinity; cell survival assays were used to measure toxicity; and cAMP assays were performed to measure receptor activation. Competitive binding results indicated that CTCUR binds to both AR A2A and AR A2B with Ki values of 5 µM and 7 µM, respectively, which is consistent with our docking results. Fluorescence microscopy data also shows binding for A2B and A2A. Cell survival results show that CTCUR and CUR are nontoxic at the tested concentrations in these cell lines. Overall, our results suggest that vanilloid phytochemicals may be slightly modified to increase interaction with Gs-ARs, and thereby can be further explored to provide a novel class of non-opioid antinociceptives.
The FASEB Journal, May 1, 2022
Pharmaceuticals
Adenosine receptors (ARs) are being explored to generate non-opioid pain therapeutics. Vanilloid ... more Adenosine receptors (ARs) are being explored to generate non-opioid pain therapeutics. Vanilloid compounds, curcumin, capsaicin, and vanillin possess antinociceptive properties through their interactions with the transient receptor potential channel family. However, their binding with adenosine receptors has not been well studied. The hypothesis in this study was that a vanilloid compound, cis-trans curcumin (CTCUR), binds to each of the two Gi-linked AR subtypes (A1AR and A3AR). CTCUR was synthesized from curcumin (CUR) using the cavitand-mediated photoisomerization technique. The cell lines transfected with the specific receptor (A1AR or A3AR) were treated with CTCUR or CUR and the binding was analyzed using competitive assays, confocal microscopy, and docking. The binding assays and molecular docking indicated that CTCUR had Ki values of 306 nM (A1AR) and 400 nM (A3AR). These values suggest that CTCUR is selective for Gi-linked ARs (A1AR or A3AR) over Gs-linked ARs (A2AAR or A2BA...
Journal of Molecular Structure
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
1. SCIENTIFIC SUMMARY The third year of research supported by ACS-PRF resulted in exploration of ... more 1. SCIENTIFIC SUMMARY The third year of research supported by ACS-PRF resulted in exploration of two different groups of alkenes for homoand heterodimerization: (a) extended and cross conjugated diene systems (dibenzylidene acetones), and unsymmetrical chalcones (phenyl styryl ketones). These new class of photosubstrates were explored to understand the excited-state photocycloaddition (PCA) characteristics of the alkenes. In both cases native efficiency of PCA is significantly lower in solution phase and solid state, and several PCA products are possible. Complexing the photoreactants to γ-cyclodextrin (γ-CD) increases PCA efficiency resulting formation of a single product. Investigation of the photochemical and photophysical features of the host-guest complex, evaluation of its association constants experimentally, and computational analysis of the complex structures provided insight into the nature of weak interactions involving aromatic groups and excited state reactivity of such...
Photocycloaddition (PCA) of alkenes is an important reaction as it is used in several areas of fu... more Photocycloaddition (PCA) of alkenes is an important reaction as it is used in several areas of fundamental and applied research. Due to its significance, there are numerous articles and reviews in chemical literature that document various aspect of this reaction -such as application in synthesis, photopolymerization, materials research, etc. Despite its importance, the vast majority of the reports are focused on the reaction between identical alkenes (homo-dimerization), while PCA between non-identical alkenes (cross-dimerization) has been grossly under-explored. In this review we have complied the reports on cross-dimerization reactions affected through supramolecular methods, which can be broadly classified based on two broad approaches: (a) crystal-engineering or (b) templation in solution or slurry. Both methods are based on the utilization of favorable intermolecular interaction between non-identical alkenes, and the use of a templating agent that promotes heteroalkene arrangement in the ground state, which, upon photoexcitation yield the cross-dimer selectively.
Pharmacological Research, 2021
All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacol... more All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacologists to generate new therapeutics for chronic pain. The vanilloid phytochemicals, which include curcumin, capsaicin, and gingerol, have been shown to alleviate pain. However, there is little to no literature on the interaction of vanilloid phytochemicals with ARs. In this study, photochemical methods were used to generate a novel isomer of curcumin (cis-trans curcumin or CTCUR), and the interactions of both curcumin and CTCUR with the two Gs-linked AR subtypes were studied. Competitive binding assays, docking analysis, and confocal fluorescence microscopy were performed to measure binding affinity; cell survival assays were used to measure toxicity; and cAMP assays were performed to measure receptor activation. Competitive binding results indicated that CTCUR binds to both AR A2A and AR A2B with Ki values of 5 µM and 7 µM, respectively, which is consistent with our docking results. Fluorescence microscopy data also shows binding for A2B and A2A. Cell survival results show that CTCUR and CUR are nontoxic at the tested concentrations in these cell lines. Overall, our results suggest that vanilloid phytochemicals may be slightly modified to increase interaction with Gs-ARs, and thereby can be further explored to provide a novel class of non-opioid antinociceptives.
Journal of the American Chemical Society, 1993
Regioselectivity and stereoselectivity in organic photochemistry continue to be topics of great i... more Regioselectivity and stereoselectivity in organic photochemistry continue to be topics of great interest. In recent years, such selectivity has been achieved to a considerable extent in photochemical processes carried out in constrained media.1" Of particular interest are the remarkable results obtained in zeolites. Zeolites have recently been shown to exert a significant influence on the unimolecular photoreactivity of included guest molecules, as in Norrish Type I and Type I1 photoreactions.7 In the area of bimolecular photoprocesses, zeolites have been shown to influence the course of [2 + 21 photodimerization of acenaphthylene,* but no such studies have been reported for [2 + 21 photocycloaddition reactions of enones, a reaction of recognized mechanistic importan~e.~ In an initial foray in this area, the effects of zeolites on photodimerizations of cyclopentenone (1) and cyclohexenone (2) have been investigated. Little control over the regiochemistry of such reactions is attainable when they are carried out in isotropic solvents.lOJ1 In this report, we show that a relatively high degree of regioselectivity in enone photodimerization can be achieved in zeolites, due to size constriction effects in the supercages of X-and Y-type faujasites as well as the complexing ability of the charge-compensating cation of the zeolite on included guests. (1) Photochemistry in micelles: (a) Thomas,
Journal of Photochemistry and Photobiology A: Chemistry, 2021
The supramolecular photocycloaddition (PCA) of 3-(phenyl)acrylic acid has been extensively pursue... more The supramolecular photocycloaddition (PCA) of 3-(phenyl)acrylic acid has been extensively pursued by chemists to study weak interactions and synthesize substituted cyclobutanes. The stereo- and regioselectivity of the products in a supramolecularly affected reaction are often used as a probe for assessing the nature of weak interactions and/or molecular ambience of the reactants. However, some crucial aspects of this chemistry have often remained underexplored in the past, especially within the context of interpreting strength and directionality of interactions based on reaction outcomes. We present a detailed study of the cavitand-mediated PCA of a new and suitable reactant (3-(naphthyl)acrylic acids) that exhibits labile photo-reversible chemistry, which is suitable for exploring previously un-explored aspects of the supramolecular PCA chemistry. Our studies afford important insights about this chemistry that should be considered while using product selectivity as a proxy for deducing intermolecular interactions.
Molecules
Singlet oxygen (1O2) is the excited state electronic isomer and a reactive form of molecular oxyg... more Singlet oxygen (1O2) is the excited state electronic isomer and a reactive form of molecular oxygen, which is most efficiently produced through the photosensitized excitation of ambient triplet oxygen. Photochemical singlet oxygen generation (SOG) has received tremendous attention historically, both for its practical application as well as for the fundamental aspects of its reactivity. Applications of singlet oxygen in medicine, wastewater treatment, microbial disinfection, and synthetic chemistry are the direct results of active past research into this reaction. Such advancements were achieved through design factors focused predominantly on the photosensitizer (PS), whose photoactivity is relegated to self-regulated structure and energetics in ground and excited states. However, the relatively new supramolecular approach of dictating molecular structure through non-bonding interactions has allowed photochemists to render otherwise inactive or less effective PSs as efficient 1O2 gen...
Nutrients
Fulminant hepatic failure (FHF) is a rare, life-threatening liver disease with a poor prognosis. ... more Fulminant hepatic failure (FHF) is a rare, life-threatening liver disease with a poor prognosis. Administration of D-galactosamine (GalN) and lipopolysaccharide (LPS) triggers acute liver injury in mice, simulating many clinical features of FHF in humans; therefore, this disease model is often used to investigate potential therapeutic interventions to treat FHF. Recently, suppression of the nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome, was shown to alleviate the severity of GalN/LPS-induced liver damage in mice. Therefore, the goal of this study was to find dietary exosome-like nanoparticles (ELNs) with therapeutic potential in curbing FHF by suppressing the NLRP3 inflammasome. Seven commonly consumed mushrooms were used to extract ELNs. These mushrooms were found to contain ELNs composed of RNAs, proteins, and lipids. Among these mushroom-derived ELNs, only shiitake mushroom-derived ELNs (S-ELNs) substantiall...