Dhiman Sarkar - Academia.edu (original) (raw)
Papers by Dhiman Sarkar
Journal of Molecular Biomarkers & Diagnosis, Jun 20, 2013
European journal of medicinal chemistry, Oct 1, 2016
The design, synthesis and antimicrobial evaluation of a novel series of azaspiro analogues of lin... more The design, synthesis and antimicrobial evaluation of a novel series of azaspiro analogues of linezolid (1) have been described. Linezolid comprises of a morpholine ring which is known for its metabolism-related liabilities. Therefore, the key modification made in the linezolid structure was the replacement of morpholine moiety with its bioisostere, 2-oxa-6-azaspiro[3.3]heptane. Furthermore, the replacement of N-acetyl terminal of 1 with various aromatic or aliphatic functionalities was carried out. The title compounds were evaluated against a panel of Gram-positive and Gram-negative bacteria and Mycobacterium tuberculosis. Subsequent structure-activity relationship (SAR) studies identified several compounds with mixed antibacterial and antitubercular profiles. Compound 22 (IC50 0.72, 0.51, 0.88, 0.49 μg/mL for Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, respectively) exhibited similar antibacterial profile as 1. The N-acetyl derivative 18 was similar to 1 in antitubercular profile. Thus, the present study successfully demonstrated the use of azaspiro substructure in the medicinal chemistry of antibacterial and antitubercular agents.
ChemistrySelect, Dec 14, 2018
A series of novel 2,5-disubstitued 1,3,4-oxadiazole derivatives bearing 2,2-dimethyl-2,3-dihydrob... more A series of novel 2,5-disubstitued 1,3,4-oxadiazole derivatives bearing 2,2-dimethyl-2,3-dihydrobenzofuran scaffold has been synthesized and screened for antitubercular activity. All the synthesized compounds were characterized by IR, 1 H NMR, 13 C-NMR and Mass spectral study. The in vitro antitubercular activity of the synthesized compounds was evaluated against Mycobacterium tuberculosis H 37 Ra(ATCC 25177) strain. Among the synthesized compounds, four compound displayed good antitubercular activity IC 50 values in low micro-gram range (< 10 μg/mL). The antitubercular data suggested that growth inhibition MTB can be imparted by the introduction of a 4trifluoromethyl phenyl acetylene substituent. Specificity of these compounds was checked by screening them for their anti-bacterial activity against four bacterial strains (Gramnegative strains: E. coli, S. aureus; Gram-positive strains: P. aeruginosa and B. subtilis). None of the compound displayed antibacterial activity against any of the seleted strain. Molecular docking studies were carried out on InhA (FabI/ENR) which shows that the synthesized compounds bind at the catalytic site in a most favourable manner suggesting their potential as anti-mycobacterial agents. The research presented here was found to be adventitious for the development of new therapeutic agents against Mycobacterium infection.
ChemistrySelect, Sep 3, 2018
Research on Chemical Intermediates, May 31, 2018
The synthesis of a new series of triazole-biscoumarin conjugates by using a molecular hybridizati... more The synthesis of a new series of triazole-biscoumarin conjugates by using a molecular hybridization approach is described. The newly synthesized compounds 6a–k were evaluated for their in vitro antitubercular activity against active and dormant Mtb H37Ra and anti-oxidant activity against DPPH radical scavenging. Molecular docking simulations for the antitubercular activity showed that the conjugates 6a–k bind in the pocket of the DprE1 enzyme. Most of the conjugates displayed good antitubercular activity against both the active and dormant Mtb H37Ra strain. The compound 6h displayed very good antitubercular activity against dormant Mtb H37Ra with an IC50 value of 1.44 μg/mL. Most of the synthesized conjugates exhibit excellent anti-oxidant activity with an IC50 of less than the standard BHT. Compound 6b is the most active among all the conjugates with an IC50 value of 08.17 ± 0.11 μg/mL. The molecular docking study shows good agreement between the observed antitubercular activity and the binding affinity.Graphical Abstract
Methods in pharmacology and toxicology, 2021
The current crisis of coronavirus pandemic has created an urgent need for readily available scien... more The current crisis of coronavirus pandemic has created an urgent need for readily available scientific information to the researchers, students, professionals, and journalists. The scientific information for the research is costly, and most of the universities and research institutes cannot afford to subscribe to all the coronavirus-related journals/articles during this crisis time. In order to expedite the process of vaccine development and discovery of anti-COVID drugs, most of the pharmaceutical companies, research institutes and publishers are playing a key role and working on war footing to get either a vaccine or an anti-COVID drug as early as possible. The collective efforts are required from everyone in this testing time of the corona crisis. To provide our contribution to the scientific community, we have made here an attempt to give an overview of some of the tools and resources freely available that probably provide some insights in data mining and screening of novel lead molecules toward coronavirus. We have collected and compiled the information of open access online tools and antiviral databases essential for the discovery and development of corona vaccine and anti-COVID drugs. The open access tools include Open Educational Resources (OERs), Google cloud, online prediction server, web-based viewer, etc., while the antiviral databases include libraries of synthetic and untested compounds, antiviral drug databases, antiviral peptides, etc. The information presented in this chapter will help the researchers to use them directly in their projects of coronavirus drug discovery.
Molecular Diversity, Aug 4, 2021
The dormant or latent form of Mycobacterium tuberculosis (MTB) is not killed by the conventional ... more The dormant or latent form of Mycobacterium tuberculosis (MTB) is not killed by the conventional antitubercular drugs. The treatment of latent TB is essential to reduce the period of treatment as well as incidences of drug resistance. In this background, we have made an attempt to develop the quantitative structure-activity relationship models (QSAR: regression and classification based) against the dormant form of MTB and later used the developed classifier models (linear discriminant analysis (LDA) and random forest (RF)) for the two-fold classifications. The logic of applying this concept of two-fold classification for the MTB modeling is to increase the confidence of correct classification. The 2D-QSAR modeling suggested the contribution of burden eigen, edge adjacency, van der Waals (vdW) surface area, topological charge, and pharmacophoric indices in predicting the antitubercular activity against the dormant MTB. The prediction qualities of the training and test sets were found to be moderate and good, according to the mean absolute error (MAE)-based criteria's. The LDA and RF models unveiled the importance of burden eigen, edge adjacency, Geary autocorrelation, and drug-like indices as discriminating features to differentiate the antitubercular compounds into higher and lower active groups. The LDA model showed the classification accuracies of 85.14% and 87.10% for the training and test sets, while the RF model exhibited the accuracies of 100.00% and 80.65% for both the sets. The descriptors selected in the final models are only two-dimensional (2D), which are easy to compute and does not require computationally expensive steps of structure conversion, optimization, and energy minimization mandatorily needed before the computation of 3D descriptors. These models could be used for identifying and selection of higher active compounds against the dormant form of the MTB.
Letters in Drug Design & Discovery, 2019
Background: Treating tuberculosis is a challenge due to the development of drug resistance. Hence... more Background: Treating tuberculosis is a challenge due to the development of drug resistance. Hence, it is imperative to develop novel leads having high potency and efficacy to curb drug resistance. Methods: The present research work is focused on microwave-assisted synthesis of novel twenty-six 3-amino-N’-benzylidenepyrazine-2-carbohydrazide derivatives (3a-z), where, lyophilization technique was used for isolation of the major intermediate, 3-aminopyrazin-2-carbohydrazide. All synthesized compounds were subjected for anti-tubercular screening against Mycobacterium tuberculosis H37Ra by using XTT Reduction Menadione Assay (XRMA) protocol. Results: Out of 26 synthesized compounds, four N’-substitutedbenzaldehyde-3-amino-pyrazine-2- carbohydrazide derivatives viz. 3i, 3j 3v and 3z showed significant activity against M. tuberculosis H37Ra. The compounds 3i, 3j, 3v and 3z showed 99, 98, 92 and 87 % inhibition respectively as compared to 94% inhibition shown by the standard drug rifampici...
Bioorganic Chemistry, 2019
Click chemistry based multicomponent approach in the synthesis of spirochromenocarbazole tethered... more Click chemistry based multicomponent approach in the synthesis of spirochromenocarbazole tethered 1,2,3-triazoles as potential anticancer agents, Bioorganic Chemistry (2019), doi:
Asian Journal of Organic and Medicinal Chemistry, 2018
Drug Development Research, Aug 20, 2021
Drug resistance in tuberculosis poses a serious threat to humanity because currently available an... more Drug resistance in tuberculosis poses a serious threat to humanity because currently available antitubercular drugs are ineffective against Mycobacterium tuberculosis (M. tuberculosis). As a result, the approval of Bedaquiline and Delamanid for the treatment of drug‐resistant tuberculosis was accelerated. Still, there is an urgent need to search for new antitubercular drugs with novel mechanisms of action (MoA). Due to this, we have designed a synthetic strategy by utilizing microwave‐assisted organic synthesis. We have compared our method with the conventional procedure, and the data show that our procedure is more effective in the preparation of title compounds. A unique series of 1‐(2‐(furan‐2‐yl)‐5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐3(2H)‐yl)‐3‐(aryl)‐prop‐2‐en‐1‐ones (5a‐o) was synthesized utilizing conventional and microwave‐assisted techniques. Synthetic compounds were investigated for antitubercular activity against Mycobacterium TB H37Ra and Mycobacterium bovis (M. bovis). Compound 5b was reported to be the most effective against M. tuberculosis H37Ra (97.69 percent inhibition at 30 μg/ml) and M. bovis (97.09 percent inhibition at 30 μg/ml). An in silico binding affinity study of mycobacterial enoyl‐acyl carrier protein reductase (InhA) reveals the binding mechanism and thermodynamic interactions that determine these molecule's binding affinity. Compound 5b had a high glide score of −8.991 and low glide energy of −49.893 kcal/mol.
Journal of Microbiological Methods, Sep 1, 2019
The antitubercular drug development pipeline could start with an in vitro investigation of severa... more The antitubercular drug development pipeline could start with an in vitro investigation of several compounds to examine their effect on active and dormant state Mycobacterium tuberculosis (Mtb). However, in vitro screening of dormant state bacilli cannot provide enough information on the simultaneous effect of a compound on the host. Therefore, we developed a live cell fluorescence based screening protocol by utilizing the high content system for determining the effect of inhibitors against active and dormant state intracellular mycobacteria. THP-1 macrophages infected with an actively growing and hypoxia derived dormant Mtb culture were standardized to develop the screening protocol. The signal to noise ratio and the Z′ factor of this assay were found to be 7.5-29 and 0.6-0.8, respectively, which confirm the robustness of the protocol. The protocol was then validated with standard inhibitors. This newly developed drug screening assay offers an easy, safe, image based high content screening tool to search for novel antitubercular inhibitors against both active and dormant state intracellular mycobacteria. Therefore, this assay could fill in the gap between in vitro and in vivo latent tuberculosis drug screening programs.
European journal of medicinal chemistry, Sep 1, 2019
Synthesis and biological evaluation of 2,4,5-trisubstituted thiazoles as antituberculosis agents ... more Synthesis and biological evaluation of 2,4,5-trisubstituted thiazoles as antituberculosis agents effective against drug-resistant tuberculosis,
Bioorganic & Medicinal Chemistry Letters, May 1, 2016
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Synthesis and docking studies of pyrazine-thiazolidinone hybrid scaffold targeting dormant tuberculosis.
ChemistrySelect, Jul 3, 2023
Neuropilin-1 (NRP-1) is a co-receptor of VEGFR (vascular endothelial growth factor receptor), but... more Neuropilin-1 (NRP-1) is a co-receptor of VEGFR (vascular endothelial growth factor receptor), but it is also suggested that NRP-1 in tumour cells may serve as a separate receptor for VEGF 165. Therefore molecules interfering with VEGF 165 binding to NRP-1 seem to be promising candidates as new anti-angiogenic and anti-tumour drugs. Here, we report the design, synthesis, biological evaluation and molecular modelling of the small cyclic peptide, which shows a good inhibitory effect on VEGF 165 /NRP-1 binding (IC 50 = 0.18 lM). The reported compound could be considered as one of the smallest cyclic peptides (MW = 510) interfering with VEGF 165 /NRP-1 binding presented up to now.
![Research paper thumbnail of Microwave-Assisted Synthesis and Antituberculosis Screening of Some 4-((3-(Trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a ]pyrazin-7(8H )-l)methyl)benzenamine Hybrids](https://attachments.academia-assets.com/112702787/thumbnails/1.jpg)
](Journal of Heterocyclic Chemistry, Nov 22, 2018
In the present investigation, a series of 4-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3... more In the present investigation, a series of 4-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)benzenamine analogs 6a-o were synthesized and characterized by IR, NMR (1 H and 13 C), and mass spectra. All newly synthesized compounds 6a-o were prepared under conventional and microwave irradiation methods. These compounds obtained in higher yields and in shorter reaction times in the microwave irradiation method when compared with the conventional method. Synthesized compounds 6a-o were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis H 37 Ra using an established XTT reduction menadione assay. Among the screened compounds, 6i (IC 50 : 1.82 μg/mL), 6j (IC 50 : 1.02 μg/mL), and 6k (IC 50 : 1.59 μg/mL) showed excellent activity. Furthermore, compound 6i showed MIC 90 value of 16.02 μg/mL. In summary, the results indicate the identification of some novel, selective, and specific inhibitors against M. tuberculosis that can be explored further for the potential antitubercular drug.
International Journal of Biological Macromolecules
Organic & Biomolecular Chemistry
Synthesis, stereo assignment and NMR based three-dimensional conformation of depsipeptide Icosali... more Synthesis, stereo assignment and NMR based three-dimensional conformation of depsipeptide Icosalide A were achieved. SAR study of Icosalide A and its analogues varying in β-hydroxy acids was investigated, further establishing their antituberculosis and anticancer activity.
International Journal of Biological Macromolecules
Journal of Molecular Biomarkers & Diagnosis, Jun 20, 2013
European journal of medicinal chemistry, Oct 1, 2016
The design, synthesis and antimicrobial evaluation of a novel series of azaspiro analogues of lin... more The design, synthesis and antimicrobial evaluation of a novel series of azaspiro analogues of linezolid (1) have been described. Linezolid comprises of a morpholine ring which is known for its metabolism-related liabilities. Therefore, the key modification made in the linezolid structure was the replacement of morpholine moiety with its bioisostere, 2-oxa-6-azaspiro[3.3]heptane. Furthermore, the replacement of N-acetyl terminal of 1 with various aromatic or aliphatic functionalities was carried out. The title compounds were evaluated against a panel of Gram-positive and Gram-negative bacteria and Mycobacterium tuberculosis. Subsequent structure-activity relationship (SAR) studies identified several compounds with mixed antibacterial and antitubercular profiles. Compound 22 (IC50 0.72, 0.51, 0.88, 0.49 μg/mL for Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, respectively) exhibited similar antibacterial profile as 1. The N-acetyl derivative 18 was similar to 1 in antitubercular profile. Thus, the present study successfully demonstrated the use of azaspiro substructure in the medicinal chemistry of antibacterial and antitubercular agents.
ChemistrySelect, Dec 14, 2018
A series of novel 2,5-disubstitued 1,3,4-oxadiazole derivatives bearing 2,2-dimethyl-2,3-dihydrob... more A series of novel 2,5-disubstitued 1,3,4-oxadiazole derivatives bearing 2,2-dimethyl-2,3-dihydrobenzofuran scaffold has been synthesized and screened for antitubercular activity. All the synthesized compounds were characterized by IR, 1 H NMR, 13 C-NMR and Mass spectral study. The in vitro antitubercular activity of the synthesized compounds was evaluated against Mycobacterium tuberculosis H 37 Ra(ATCC 25177) strain. Among the synthesized compounds, four compound displayed good antitubercular activity IC 50 values in low micro-gram range (< 10 μg/mL). The antitubercular data suggested that growth inhibition MTB can be imparted by the introduction of a 4trifluoromethyl phenyl acetylene substituent. Specificity of these compounds was checked by screening them for their anti-bacterial activity against four bacterial strains (Gramnegative strains: E. coli, S. aureus; Gram-positive strains: P. aeruginosa and B. subtilis). None of the compound displayed antibacterial activity against any of the seleted strain. Molecular docking studies were carried out on InhA (FabI/ENR) which shows that the synthesized compounds bind at the catalytic site in a most favourable manner suggesting their potential as anti-mycobacterial agents. The research presented here was found to be adventitious for the development of new therapeutic agents against Mycobacterium infection.
ChemistrySelect, Sep 3, 2018
Research on Chemical Intermediates, May 31, 2018
The synthesis of a new series of triazole-biscoumarin conjugates by using a molecular hybridizati... more The synthesis of a new series of triazole-biscoumarin conjugates by using a molecular hybridization approach is described. The newly synthesized compounds 6a–k were evaluated for their in vitro antitubercular activity against active and dormant Mtb H37Ra and anti-oxidant activity against DPPH radical scavenging. Molecular docking simulations for the antitubercular activity showed that the conjugates 6a–k bind in the pocket of the DprE1 enzyme. Most of the conjugates displayed good antitubercular activity against both the active and dormant Mtb H37Ra strain. The compound 6h displayed very good antitubercular activity against dormant Mtb H37Ra with an IC50 value of 1.44 μg/mL. Most of the synthesized conjugates exhibit excellent anti-oxidant activity with an IC50 of less than the standard BHT. Compound 6b is the most active among all the conjugates with an IC50 value of 08.17 ± 0.11 μg/mL. The molecular docking study shows good agreement between the observed antitubercular activity and the binding affinity.Graphical Abstract
Methods in pharmacology and toxicology, 2021
The current crisis of coronavirus pandemic has created an urgent need for readily available scien... more The current crisis of coronavirus pandemic has created an urgent need for readily available scientific information to the researchers, students, professionals, and journalists. The scientific information for the research is costly, and most of the universities and research institutes cannot afford to subscribe to all the coronavirus-related journals/articles during this crisis time. In order to expedite the process of vaccine development and discovery of anti-COVID drugs, most of the pharmaceutical companies, research institutes and publishers are playing a key role and working on war footing to get either a vaccine or an anti-COVID drug as early as possible. The collective efforts are required from everyone in this testing time of the corona crisis. To provide our contribution to the scientific community, we have made here an attempt to give an overview of some of the tools and resources freely available that probably provide some insights in data mining and screening of novel lead molecules toward coronavirus. We have collected and compiled the information of open access online tools and antiviral databases essential for the discovery and development of corona vaccine and anti-COVID drugs. The open access tools include Open Educational Resources (OERs), Google cloud, online prediction server, web-based viewer, etc., while the antiviral databases include libraries of synthetic and untested compounds, antiviral drug databases, antiviral peptides, etc. The information presented in this chapter will help the researchers to use them directly in their projects of coronavirus drug discovery.
Molecular Diversity, Aug 4, 2021
The dormant or latent form of Mycobacterium tuberculosis (MTB) is not killed by the conventional ... more The dormant or latent form of Mycobacterium tuberculosis (MTB) is not killed by the conventional antitubercular drugs. The treatment of latent TB is essential to reduce the period of treatment as well as incidences of drug resistance. In this background, we have made an attempt to develop the quantitative structure-activity relationship models (QSAR: regression and classification based) against the dormant form of MTB and later used the developed classifier models (linear discriminant analysis (LDA) and random forest (RF)) for the two-fold classifications. The logic of applying this concept of two-fold classification for the MTB modeling is to increase the confidence of correct classification. The 2D-QSAR modeling suggested the contribution of burden eigen, edge adjacency, van der Waals (vdW) surface area, topological charge, and pharmacophoric indices in predicting the antitubercular activity against the dormant MTB. The prediction qualities of the training and test sets were found to be moderate and good, according to the mean absolute error (MAE)-based criteria's. The LDA and RF models unveiled the importance of burden eigen, edge adjacency, Geary autocorrelation, and drug-like indices as discriminating features to differentiate the antitubercular compounds into higher and lower active groups. The LDA model showed the classification accuracies of 85.14% and 87.10% for the training and test sets, while the RF model exhibited the accuracies of 100.00% and 80.65% for both the sets. The descriptors selected in the final models are only two-dimensional (2D), which are easy to compute and does not require computationally expensive steps of structure conversion, optimization, and energy minimization mandatorily needed before the computation of 3D descriptors. These models could be used for identifying and selection of higher active compounds against the dormant form of the MTB.
Letters in Drug Design & Discovery, 2019
Background: Treating tuberculosis is a challenge due to the development of drug resistance. Hence... more Background: Treating tuberculosis is a challenge due to the development of drug resistance. Hence, it is imperative to develop novel leads having high potency and efficacy to curb drug resistance. Methods: The present research work is focused on microwave-assisted synthesis of novel twenty-six 3-amino-N’-benzylidenepyrazine-2-carbohydrazide derivatives (3a-z), where, lyophilization technique was used for isolation of the major intermediate, 3-aminopyrazin-2-carbohydrazide. All synthesized compounds were subjected for anti-tubercular screening against Mycobacterium tuberculosis H37Ra by using XTT Reduction Menadione Assay (XRMA) protocol. Results: Out of 26 synthesized compounds, four N’-substitutedbenzaldehyde-3-amino-pyrazine-2- carbohydrazide derivatives viz. 3i, 3j 3v and 3z showed significant activity against M. tuberculosis H37Ra. The compounds 3i, 3j, 3v and 3z showed 99, 98, 92 and 87 % inhibition respectively as compared to 94% inhibition shown by the standard drug rifampici...
Bioorganic Chemistry, 2019
Click chemistry based multicomponent approach in the synthesis of spirochromenocarbazole tethered... more Click chemistry based multicomponent approach in the synthesis of spirochromenocarbazole tethered 1,2,3-triazoles as potential anticancer agents, Bioorganic Chemistry (2019), doi:
Asian Journal of Organic and Medicinal Chemistry, 2018
Drug Development Research, Aug 20, 2021
Drug resistance in tuberculosis poses a serious threat to humanity because currently available an... more Drug resistance in tuberculosis poses a serious threat to humanity because currently available antitubercular drugs are ineffective against Mycobacterium tuberculosis (M. tuberculosis). As a result, the approval of Bedaquiline and Delamanid for the treatment of drug‐resistant tuberculosis was accelerated. Still, there is an urgent need to search for new antitubercular drugs with novel mechanisms of action (MoA). Due to this, we have designed a synthetic strategy by utilizing microwave‐assisted organic synthesis. We have compared our method with the conventional procedure, and the data show that our procedure is more effective in the preparation of title compounds. A unique series of 1‐(2‐(furan‐2‐yl)‐5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐3(2H)‐yl)‐3‐(aryl)‐prop‐2‐en‐1‐ones (5a‐o) was synthesized utilizing conventional and microwave‐assisted techniques. Synthetic compounds were investigated for antitubercular activity against Mycobacterium TB H37Ra and Mycobacterium bovis (M. bovis). Compound 5b was reported to be the most effective against M. tuberculosis H37Ra (97.69 percent inhibition at 30 μg/ml) and M. bovis (97.09 percent inhibition at 30 μg/ml). An in silico binding affinity study of mycobacterial enoyl‐acyl carrier protein reductase (InhA) reveals the binding mechanism and thermodynamic interactions that determine these molecule's binding affinity. Compound 5b had a high glide score of −8.991 and low glide energy of −49.893 kcal/mol.
Journal of Microbiological Methods, Sep 1, 2019
The antitubercular drug development pipeline could start with an in vitro investigation of severa... more The antitubercular drug development pipeline could start with an in vitro investigation of several compounds to examine their effect on active and dormant state Mycobacterium tuberculosis (Mtb). However, in vitro screening of dormant state bacilli cannot provide enough information on the simultaneous effect of a compound on the host. Therefore, we developed a live cell fluorescence based screening protocol by utilizing the high content system for determining the effect of inhibitors against active and dormant state intracellular mycobacteria. THP-1 macrophages infected with an actively growing and hypoxia derived dormant Mtb culture were standardized to develop the screening protocol. The signal to noise ratio and the Z′ factor of this assay were found to be 7.5-29 and 0.6-0.8, respectively, which confirm the robustness of the protocol. The protocol was then validated with standard inhibitors. This newly developed drug screening assay offers an easy, safe, image based high content screening tool to search for novel antitubercular inhibitors against both active and dormant state intracellular mycobacteria. Therefore, this assay could fill in the gap between in vitro and in vivo latent tuberculosis drug screening programs.
European journal of medicinal chemistry, Sep 1, 2019
Synthesis and biological evaluation of 2,4,5-trisubstituted thiazoles as antituberculosis agents ... more Synthesis and biological evaluation of 2,4,5-trisubstituted thiazoles as antituberculosis agents effective against drug-resistant tuberculosis,
Bioorganic & Medicinal Chemistry Letters, May 1, 2016
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Synthesis and docking studies of pyrazine-thiazolidinone hybrid scaffold targeting dormant tuberculosis.
ChemistrySelect, Jul 3, 2023
Neuropilin-1 (NRP-1) is a co-receptor of VEGFR (vascular endothelial growth factor receptor), but... more Neuropilin-1 (NRP-1) is a co-receptor of VEGFR (vascular endothelial growth factor receptor), but it is also suggested that NRP-1 in tumour cells may serve as a separate receptor for VEGF 165. Therefore molecules interfering with VEGF 165 binding to NRP-1 seem to be promising candidates as new anti-angiogenic and anti-tumour drugs. Here, we report the design, synthesis, biological evaluation and molecular modelling of the small cyclic peptide, which shows a good inhibitory effect on VEGF 165 /NRP-1 binding (IC 50 = 0.18 lM). The reported compound could be considered as one of the smallest cyclic peptides (MW = 510) interfering with VEGF 165 /NRP-1 binding presented up to now.
Journal of Heterocyclic Chemistry, Nov 22, 2018
In the present investigation, a series of 4-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3... more In the present investigation, a series of 4-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)benzenamine analogs 6a-o were synthesized and characterized by IR, NMR (1 H and 13 C), and mass spectra. All newly synthesized compounds 6a-o were prepared under conventional and microwave irradiation methods. These compounds obtained in higher yields and in shorter reaction times in the microwave irradiation method when compared with the conventional method. Synthesized compounds 6a-o were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis H 37 Ra using an established XTT reduction menadione assay. Among the screened compounds, 6i (IC 50 : 1.82 μg/mL), 6j (IC 50 : 1.02 μg/mL), and 6k (IC 50 : 1.59 μg/mL) showed excellent activity. Furthermore, compound 6i showed MIC 90 value of 16.02 μg/mL. In summary, the results indicate the identification of some novel, selective, and specific inhibitors against M. tuberculosis that can be explored further for the potential antitubercular drug.
International Journal of Biological Macromolecules
Organic & Biomolecular Chemistry
Synthesis, stereo assignment and NMR based three-dimensional conformation of depsipeptide Icosali... more Synthesis, stereo assignment and NMR based three-dimensional conformation of depsipeptide Icosalide A were achieved. SAR study of Icosalide A and its analogues varying in β-hydroxy acids was investigated, further establishing their antituberculosis and anticancer activity.
International Journal of Biological Macromolecules