Abdul Wadood - Academia.edu (original) (raw)

Papers by Abdul Wadood

Research paper thumbnail of Design of New and Potent Diethyl Thiobarbiturates as Urease Inhibitors: A Computational Approach

Bioinformation, 2014

Urease is an important enzyme both in agriculture and medicine research. Strategies based on urea... more Urease is an important enzyme both in agriculture and medicine research. Strategies based on urease inhibition is critically considered as the first line treatment of infections caused by urease producing bacteria. Since, urease possess agro-chemical and medicinal importance, thus, it is necessary to search for the novel compounds capable of inhibiting this enzyme. Several computational methods were employed to design novel and potent urease inhibitors in this work. First docking simulations of known compounds consists of a set of arylidine barbiturates (termed as reference) were performed on the Bacillus pasteurii (BP) urease. Subsequently, two fold strategies were used to design new compounds against urease. Stage 1 comprised of the energy minimization of enzyme-ligand complexes of reference compounds and the accurate prediction of the molecular mechanics generalized born (MMGB) interaction energies. In the second stage, new urease inhibitors were then designed by the substitution of different groups consecutively in the aryl ring of the thiobarbiturates and N, N-diethyl thiobarbiturates of the reference ligands.. The enzyme-ligand complexes with lowest interaction energies or energies close to the calculated interaction energies of the reference molecules, were selected for the consequent chemical manipulation. This was followed by the substitution of different groups on the 2 and 5 positions of the aryl ring. As a result, several new and potent diethyl thiobarbiturates were predicted as urease inhibitors. This approach reflects a logical progression for early stage drug discovery that can be exploited to successfully identify potential drug candidates.

Research paper thumbnail of Prevalence and antibiotic susceptibility profile of methicillin resistant Staphylococcus aureus in Accra, Ghana

Microbiology Research, 2012

Over the last four decades, methicillin-resistant Staphylococcus aureus (MRSA) has spread through... more Over the last four decades, methicillin-resistant Staphylococcus aureus (MRSA) has spread throughout the world and become highly endemic in many geographical areas. This pathogen causes severe morbidity and mortality in hospitals worldwide. MRSA is also considered a major community acquired pathogen throughout the world. MRSA is implicated in serious clinical conditions such as bacteremia, pneumonia, and intra-abdominal infection. The objective of this study was to determine the prevalence of MRSA in Accra, Ghana, and also to determine its antibiotic susceptibility profile. Two hundred and fifty Staphylococcus aureus isolates from routine microbiological specimens were collected from five hospitals in Accra. MRSA screening assay was used to screen for MRSA. Disc diffusion method (Kirby-Bauer) was used to determine the susceptibility of the MRSA. The MRSA screening assay, which is very close to the polymerase chain reaction in terms of specificity and sensitivity, showed that 84 of the 250 isolates were MRSA, giving a prevalence rate of 33.6%. MRSA strains were susceptible to erythromycin; 63 out of the 84 MRSA isolates were susceptible representing 75%. This was followed by gentamicin 46 (54.7%), cotrimoxazole 35 (49%), cefuroxime 33 (38%), flucloxacillin 24 (28.6%), and ampicillin 13 (15.5%). Penicillin 4 (4.8%) and tetracycline 6 (7.1%) were the least susceptible. The findings from this study emphasize the need for continual surveillance of MRSA and of antibiotic resistance in general.

Research paper thumbnail of Thermal Performance Investigation of Slotted Fin Minichannel Heat Sink for Microprocessor Cooling

Energies

Due to high heat flux generation inside microprocessors, water-cooled heat sinks have gained spec... more Due to high heat flux generation inside microprocessors, water-cooled heat sinks have gained special attention. For the durability of the microprocessor, this generated flux should be effectively removed. The effective thermal management of high-processing devices is now becoming popular due to high heat flux generation. Heat removal plays a significant role in the longer operation and better performance of heat sinks. In this work, to tackle the heat generation issues, a slotted fin minichannel heat sink (SFMCHS) was investigated by modifying a conventional straight integral fin minichannel heat sink (SIFMCHS). SFMCHSs with fin spacings of 0.5 mm, 1 mm, and 1.5 mm were numerically studied. The numerical results were then compared with SIFMCHSs present in the literature. The base temperatures recorded for two slots per fin minichannel heat sink (SPFMCHS), with 0.5 mm, 1 mm, and 1.5 mm fin spacings, were 42.81 °C, 46.36 °C, and 48.86 °C, respectively, at 1 LPM. The reductions in base...

Research paper thumbnail of A Comparative Analysis of the Efficacy of Three Program-Evaluation Models –A Review on Their Implication in Educational Programs

Humanities & Social Sciences Reviews

Purpose of the study: This article reviews the comparative efficacy, theoretical and practical ba... more Purpose of the study: This article reviews the comparative efficacy, theoretical and practical background of three program evaluation models (Stufflebeam’s CIPP model, Kirkpatrick’s model, and outcome-based evaluation models) and their implications in educational programs. The article discusses the strengths and limitations of the three evaluation models. Methodology: Peer-reviewed and scholarly journals were searched for articles related to program evaluation models and their importance. Keywords included program evaluation’, ‘assessment’, ‘CIPP model’, ‘evaluation of educational programs, ‘outcome-based model, and ‘planning’. Articles on Stufflebeam’s CIPP model, Kirkpatrick’s model, and outcome-based evaluation models were particularlyfocused because the review aimed at analysing these three models. The strengths and inadequacies of the three models were weighed and presented. Main Findings: The three models –outcome-based evaluation model, the Kirkpatric model, and the CIPP eval...

Research paper thumbnail of Mechanism of zinc ejection by disulfiram in nonstructural protein 5A

Physical Chemistry Chemical Physics

Hepatitis C virus (HCV) is a notorious member of the Flaviviridae family of enveloped, positive-s... more Hepatitis C virus (HCV) is a notorious member of the Flaviviridae family of enveloped, positive-strand RNA viruses.

Research paper thumbnail of Structure-Based Virtual Screening of Tumor Necrosis Factor-α Inhibitors by Cheminformatics Approaches and Bio-Molecular Simulation

Biomolecules

Tumor necrosis factor-α (TNF-α) is a drug target in rheumatoid arthritis and several other auto-i... more Tumor necrosis factor-α (TNF-α) is a drug target in rheumatoid arthritis and several other auto-immune disorders. TNF-α binds with TNF receptors (TNFR), located on the surface of several immunological cells to exert its effect. Hence, the use of inhibitors that can hinder the complex formation of TNF-α/TNFR can be of medicinal significance. In this study, multiple chem-informatics approaches, including descriptor-based screening, 2D-similarity searching, and pharmacophore modelling were applied to screen new TNF-α inhibitors. Subsequently, multiple-docking protocols were used, and four-fold post-docking results were analyzed by consensus approach. After structure-based virtual screening, seventeen compounds were mutually ranked in top-ranked position by all the docking programs. Those identified hits target TNF-α dimer and effectively block TNF-α/TNFR interface. The predicted pharmacokinetics and physiological properties of the selected hits revealed that, out of seventeen, seven co...

Research paper thumbnail of Modeling Novel Putative Drugs and Vaccine Candidates against Tick-Borne Pathogens: A Subtractive Proteomics Approach

Veterinary Sciences

Ticks and tick-borne pathogens (TBPs) continuously causing substantial losses to the public and v... more Ticks and tick-borne pathogens (TBPs) continuously causing substantial losses to the public and veterinary health sectors. The identification of putative drug targets and vaccine candidates is crucial to control TBPs. No information has been recorded on designing novel drug targets and vaccine candidates based on proteins. Subtractive proteomics is an in silico approach that utilizes extensive screening for the identification of novel drug targets or vaccine candidates based on the determination of potential target proteins available in a pathogen proteome that may be used effectively to control diseases caused by these infectious agents. The present study aimed to investigate novel drug targets and vaccine candidates by utilizing subtractive proteomics to scan the available proteomes of TBPs and predict essential and non-host homologous proteins required for the survival of these diseases causing agents. Subtractive proteome analysis revealed a list of fifteen essential, non-host h...

Research paper thumbnail of Proteome-wide mapping and reverse vaccinology-based B and T cell multi-epitope subunit vaccine designing for immune response reinforcement against Porphyromonas gingivalis

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of Correction: Ali, A., et al. Modeling Novel Putative Drugs and Vaccine Candidates against Tick-Borne Pathogens: A Subtractive Proteomics Approach. Vet. Sci. 2020, 7, 129

Veterinary Sciences

The authors wish to make the following corrections to this paper [...]

Research paper thumbnail of Synthesis, in vitro urease inhibitory potential and molecular docking study of benzofuran-based-thiazoldinone analogues

Scientific Reports

in continuation of our work on enzyme inhibition, the benzofuran-based-thiazoldinone analogues (1... more in continuation of our work on enzyme inhibition, the benzofuran-based-thiazoldinone analogues (1-14) were synthesized, characterized by HREI-MS, 1 H and 13 cnMR and evaluated for urease inhibition. Compounds 1-14 exhibited a varying degree of urease inhibitory activity with IC 50 values between 1.2 ± 0.01 to 23.50 ± 0.70 µM when compared with standard drug thiourea having IC 50 value 21.40 ± 0.21 µM. Compound 1, 3, 5 and 8 showed significant inhibitory effects with IC 50 values 1.2 ± 0.01, 2.20 ± 0.01, 1.40 ± 0.01 and 2.90 ± 0.01 µM respectively, better than the rest of the series. A structure activity relationship (SAR) of this series has been established based on electronic effects and position of different substituents present on phenyl ring. Molecular docking studies were performed to understand the binding interaction of the compounds. Benzofuran scaffolds due to its profound chemotherapeutic, physiological properties and their dynamic nature has attracted the attention of chemist during last few years 1. Acting as versatile scaffolds, benzofuran derivatives can be used to synthesize potentially new therapeutic agents 2. These scaffolds exhibited biological properties such as antimicrobial 3 , analgesic 4 , anti-hyperglycemic 5 , anti-parasitic 6 , antitumor and kinase inhibitors 7. Besides these properties benzofuran scaffolds also found application as oxidant 8 , fluorescent sensor 9 , brightening agent, antioxidant and in other field of chemistry and agriculture 10. Urease is a metalloenzyme contain nickel that is responsible for catalyzing urea hydrolysis to ammonia and carbamate, the latter spontaneously hydrolyzing to carbonic acid and a second molecule of ammonia in an uncatalyzed reaction 11. Ammonia molecules thus formed are protonated by water at physiological pH, whereas the carbonic acid dissociates and causes an increase in pH.

Research paper thumbnail of In vivo anti-nociceptive potential and cyclooxygenases 1 and 2 selectivity of di-naphthodiospyrols from Diospyros lotus

Revista Brasileira de Farmacognosia

Research paper thumbnail of Aryl-oxadiazole Schiff bases: Synthesis, α-glucosidase in vitro inhibitory activity and their in silico studies

Arabian Journal of Chemistry

Research paper thumbnail of In Silico Modeling of Crimean Congo Hemorrhagic Fever Virus Glycoprotein-N and Screening of Anti Viral Hits by Virtual Screening

International Journal of Peptide Research and Therapeutics

Crimean-Congo hemorrhagic fever (CCHF) is a widespread zoonotic viral disease, caused by a tick-b... more Crimean-Congo hemorrhagic fever (CCHF) is a widespread zoonotic viral disease, caused by a tick-born virus Crimean-Congo hemorrhagic fever virus (CCHFV). This disease is endemic in Middle East, Asia, Africa and SouthEastern Europe with the mortality rate of 5-30%. CCHFV genome is composed of three segments: large, medium and small segments. M segment encodes a polyprotein (glycoprotein) so called glycoprotein N (Gn) which is considered as a potential druggable target for the effective therapy of CCHF. The complete structure of Gn is still not characterized. The aim of the current study is to predict the complete three-dimensional (3D-) structure of CCHFV Gn protein via threading-based modeling and investigate the residues crucial for binding with CCHFV envelop. The developed model displayed excellent stereo-chemical and geometrical properties. Subsequently structure based virtual screening (SBVS) was applied to discover novel inhibitors of Gn protein. A library of > 1300 anti-virals was selected from PubChem database and directed to the predicted binding site of Gn. The SBVS results led to the identification of thirty-seven compounds that inhibit the protein in computational analysis. Those 37 hits were subject to pharmacokinetic profiling which demonstrated that 30/37 compound possess safer pharmacokinetic properties. Thus, by specifically targeting Gn, less toxic and more potent inhibitors of CCHFV were identified in silico.

Research paper thumbnail of In-silico design of peptide inhibitors of K-Ras target in cancer disease

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of Theoretical and Experimental in vitro Antifungal and Antitumor Activities of Organotin(IV) Derivatives of 3-(4-nitrophenyl)-2-methylacrylic acid

Pharmaceutical Chemistry Journal

Research paper thumbnail of Synthesis, In vitro α-Amylase Inhibitory, and Radicals (DPPH ABTS) Scavenging Potentials of New N-Sulfonohydrazide Substituted Indazoles

Research paper thumbnail of Synthesis, in vitro urease inhibitory activity and molecular docking of 3,5‐disubstituted thiadiazine‐2‐thiones

Journal of Heterocyclic Chemistry

Research paper thumbnail of Synthesis of benzotriazoles derivatives and their dual potential as α-amylase and α-glucosidase inhibitors in vitro: Structure-activity relationship, molecular docking, and kinetic studies

European Journal of Medicinal Chemistry

Research paper thumbnail of Proteome-wide subtractive approach to prioritize a hypothetical protein of XDR-Mycobacterium tuberculosis as potential drug target

Genes & Genomics

Background Among the resistant isolates of MTB, multidrug resistant tuberculosis (MDR-TB) and ext... more Background Among the resistant isolates of MTB, multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) have been the areas of growing concern. The genomic analysis showed that the respective genomic pool of the XDR-MTB proteome contains more than 30% of the hypothetical proteins for which no functions have been annotated yet. This class of proteins presumably have their own importance to complete genome and proteome information. The bioinformatics advancements have helped to annotate those hypothetical proteins by using various computational tools and have potential to classify them functionally. Objective The objective of this study was to propose a new and unique drug target against the deadly Mycobacterium tuberculosis using Bioinformatics approaches to characterize the hypothetical proteins. Results We stepwise reduced the hypothetical proteins (total number: 1256) out of the complete proteome to only 26 essential hypothetical proteins. Out of those 26 proteins, the protein WP_003401246.1 was computationally characterized as the druggable target. Conclusion The study proposed a hypothetical protein from complete proteome of the XDR-MTB as a new drug target against which new drug candidates can be proposed. Hence, the study opens up the new avenues in the areas of drug discovery against deadly M. tuberculosis.

Research paper thumbnail of Synthesis, In vitro α-Glucosidase Inhibitory Potential and Molecular Docking Studies of 2-Amino-1,3,4-Oxadiazole Derivatives

Medicinal Chemistry

Background: In the recent past, we had synthesized and reported different derivatives of oxadiazo... more Background: In the recent past, we had synthesized and reported different derivatives of oxadiazoles as potential α-glucosidase inhibitors. Keeping in mind, the pharmacological aspects of oxadiazole moiety and in continuation of our ongoing research on the chemistry and bioactivity of new heterocyclic compounds. Method: 1,3,4-Oxadiazole derivatives (1-14) have been synthesized and characterized by different spectroscopic techniques such as 1H-, 13C-NMR and HREI-MS. Result: The synthetic derivatives were screened for α-glucosidase inhibitory potential, all compounds exhibited good inhibitory activity with IC50 values ranging between 0.80 ± 0.1 to 45.1 ± 1.7 μM in comparison with the standard acarbose having IC50 value 38.45 ± 0.80 μM. Conclusion: Thirteen compounds 1-6 and 8-14 showed potential inhibitory activity as compared to the standard acarbose having IC50 values 38.45 ± 0.80 μM, however, only one compound 7 (IC50 = 45.1 ± 1.7 μM) was found to be less active. Compound 14 (IC50 ...

Research paper thumbnail of Design of New and Potent Diethyl Thiobarbiturates as Urease Inhibitors: A Computational Approach

Bioinformation, 2014

Urease is an important enzyme both in agriculture and medicine research. Strategies based on urea... more Urease is an important enzyme both in agriculture and medicine research. Strategies based on urease inhibition is critically considered as the first line treatment of infections caused by urease producing bacteria. Since, urease possess agro-chemical and medicinal importance, thus, it is necessary to search for the novel compounds capable of inhibiting this enzyme. Several computational methods were employed to design novel and potent urease inhibitors in this work. First docking simulations of known compounds consists of a set of arylidine barbiturates (termed as reference) were performed on the Bacillus pasteurii (BP) urease. Subsequently, two fold strategies were used to design new compounds against urease. Stage 1 comprised of the energy minimization of enzyme-ligand complexes of reference compounds and the accurate prediction of the molecular mechanics generalized born (MMGB) interaction energies. In the second stage, new urease inhibitors were then designed by the substitution of different groups consecutively in the aryl ring of the thiobarbiturates and N, N-diethyl thiobarbiturates of the reference ligands.. The enzyme-ligand complexes with lowest interaction energies or energies close to the calculated interaction energies of the reference molecules, were selected for the consequent chemical manipulation. This was followed by the substitution of different groups on the 2 and 5 positions of the aryl ring. As a result, several new and potent diethyl thiobarbiturates were predicted as urease inhibitors. This approach reflects a logical progression for early stage drug discovery that can be exploited to successfully identify potential drug candidates.

Research paper thumbnail of Prevalence and antibiotic susceptibility profile of methicillin resistant Staphylococcus aureus in Accra, Ghana

Microbiology Research, 2012

Over the last four decades, methicillin-resistant Staphylococcus aureus (MRSA) has spread through... more Over the last four decades, methicillin-resistant Staphylococcus aureus (MRSA) has spread throughout the world and become highly endemic in many geographical areas. This pathogen causes severe morbidity and mortality in hospitals worldwide. MRSA is also considered a major community acquired pathogen throughout the world. MRSA is implicated in serious clinical conditions such as bacteremia, pneumonia, and intra-abdominal infection. The objective of this study was to determine the prevalence of MRSA in Accra, Ghana, and also to determine its antibiotic susceptibility profile. Two hundred and fifty Staphylococcus aureus isolates from routine microbiological specimens were collected from five hospitals in Accra. MRSA screening assay was used to screen for MRSA. Disc diffusion method (Kirby-Bauer) was used to determine the susceptibility of the MRSA. The MRSA screening assay, which is very close to the polymerase chain reaction in terms of specificity and sensitivity, showed that 84 of the 250 isolates were MRSA, giving a prevalence rate of 33.6%. MRSA strains were susceptible to erythromycin; 63 out of the 84 MRSA isolates were susceptible representing 75%. This was followed by gentamicin 46 (54.7%), cotrimoxazole 35 (49%), cefuroxime 33 (38%), flucloxacillin 24 (28.6%), and ampicillin 13 (15.5%). Penicillin 4 (4.8%) and tetracycline 6 (7.1%) were the least susceptible. The findings from this study emphasize the need for continual surveillance of MRSA and of antibiotic resistance in general.

Research paper thumbnail of Thermal Performance Investigation of Slotted Fin Minichannel Heat Sink for Microprocessor Cooling

Energies

Due to high heat flux generation inside microprocessors, water-cooled heat sinks have gained spec... more Due to high heat flux generation inside microprocessors, water-cooled heat sinks have gained special attention. For the durability of the microprocessor, this generated flux should be effectively removed. The effective thermal management of high-processing devices is now becoming popular due to high heat flux generation. Heat removal plays a significant role in the longer operation and better performance of heat sinks. In this work, to tackle the heat generation issues, a slotted fin minichannel heat sink (SFMCHS) was investigated by modifying a conventional straight integral fin minichannel heat sink (SIFMCHS). SFMCHSs with fin spacings of 0.5 mm, 1 mm, and 1.5 mm were numerically studied. The numerical results were then compared with SIFMCHSs present in the literature. The base temperatures recorded for two slots per fin minichannel heat sink (SPFMCHS), with 0.5 mm, 1 mm, and 1.5 mm fin spacings, were 42.81 °C, 46.36 °C, and 48.86 °C, respectively, at 1 LPM. The reductions in base...

Research paper thumbnail of A Comparative Analysis of the Efficacy of Three Program-Evaluation Models –A Review on Their Implication in Educational Programs

Humanities & Social Sciences Reviews

Purpose of the study: This article reviews the comparative efficacy, theoretical and practical ba... more Purpose of the study: This article reviews the comparative efficacy, theoretical and practical background of three program evaluation models (Stufflebeam’s CIPP model, Kirkpatrick’s model, and outcome-based evaluation models) and their implications in educational programs. The article discusses the strengths and limitations of the three evaluation models. Methodology: Peer-reviewed and scholarly journals were searched for articles related to program evaluation models and their importance. Keywords included program evaluation’, ‘assessment’, ‘CIPP model’, ‘evaluation of educational programs, ‘outcome-based model, and ‘planning’. Articles on Stufflebeam’s CIPP model, Kirkpatrick’s model, and outcome-based evaluation models were particularlyfocused because the review aimed at analysing these three models. The strengths and inadequacies of the three models were weighed and presented. Main Findings: The three models –outcome-based evaluation model, the Kirkpatric model, and the CIPP eval...

Research paper thumbnail of Mechanism of zinc ejection by disulfiram in nonstructural protein 5A

Physical Chemistry Chemical Physics

Hepatitis C virus (HCV) is a notorious member of the Flaviviridae family of enveloped, positive-s... more Hepatitis C virus (HCV) is a notorious member of the Flaviviridae family of enveloped, positive-strand RNA viruses.

Research paper thumbnail of Structure-Based Virtual Screening of Tumor Necrosis Factor-α Inhibitors by Cheminformatics Approaches and Bio-Molecular Simulation

Biomolecules

Tumor necrosis factor-α (TNF-α) is a drug target in rheumatoid arthritis and several other auto-i... more Tumor necrosis factor-α (TNF-α) is a drug target in rheumatoid arthritis and several other auto-immune disorders. TNF-α binds with TNF receptors (TNFR), located on the surface of several immunological cells to exert its effect. Hence, the use of inhibitors that can hinder the complex formation of TNF-α/TNFR can be of medicinal significance. In this study, multiple chem-informatics approaches, including descriptor-based screening, 2D-similarity searching, and pharmacophore modelling were applied to screen new TNF-α inhibitors. Subsequently, multiple-docking protocols were used, and four-fold post-docking results were analyzed by consensus approach. After structure-based virtual screening, seventeen compounds were mutually ranked in top-ranked position by all the docking programs. Those identified hits target TNF-α dimer and effectively block TNF-α/TNFR interface. The predicted pharmacokinetics and physiological properties of the selected hits revealed that, out of seventeen, seven co...

Research paper thumbnail of Modeling Novel Putative Drugs and Vaccine Candidates against Tick-Borne Pathogens: A Subtractive Proteomics Approach

Veterinary Sciences

Ticks and tick-borne pathogens (TBPs) continuously causing substantial losses to the public and v... more Ticks and tick-borne pathogens (TBPs) continuously causing substantial losses to the public and veterinary health sectors. The identification of putative drug targets and vaccine candidates is crucial to control TBPs. No information has been recorded on designing novel drug targets and vaccine candidates based on proteins. Subtractive proteomics is an in silico approach that utilizes extensive screening for the identification of novel drug targets or vaccine candidates based on the determination of potential target proteins available in a pathogen proteome that may be used effectively to control diseases caused by these infectious agents. The present study aimed to investigate novel drug targets and vaccine candidates by utilizing subtractive proteomics to scan the available proteomes of TBPs and predict essential and non-host homologous proteins required for the survival of these diseases causing agents. Subtractive proteome analysis revealed a list of fifteen essential, non-host h...

Research paper thumbnail of Proteome-wide mapping and reverse vaccinology-based B and T cell multi-epitope subunit vaccine designing for immune response reinforcement against Porphyromonas gingivalis

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of Correction: Ali, A., et al. Modeling Novel Putative Drugs and Vaccine Candidates against Tick-Borne Pathogens: A Subtractive Proteomics Approach. Vet. Sci. 2020, 7, 129

Veterinary Sciences

The authors wish to make the following corrections to this paper [...]

Research paper thumbnail of Synthesis, in vitro urease inhibitory potential and molecular docking study of benzofuran-based-thiazoldinone analogues

Scientific Reports

in continuation of our work on enzyme inhibition, the benzofuran-based-thiazoldinone analogues (1... more in continuation of our work on enzyme inhibition, the benzofuran-based-thiazoldinone analogues (1-14) were synthesized, characterized by HREI-MS, 1 H and 13 cnMR and evaluated for urease inhibition. Compounds 1-14 exhibited a varying degree of urease inhibitory activity with IC 50 values between 1.2 ± 0.01 to 23.50 ± 0.70 µM when compared with standard drug thiourea having IC 50 value 21.40 ± 0.21 µM. Compound 1, 3, 5 and 8 showed significant inhibitory effects with IC 50 values 1.2 ± 0.01, 2.20 ± 0.01, 1.40 ± 0.01 and 2.90 ± 0.01 µM respectively, better than the rest of the series. A structure activity relationship (SAR) of this series has been established based on electronic effects and position of different substituents present on phenyl ring. Molecular docking studies were performed to understand the binding interaction of the compounds. Benzofuran scaffolds due to its profound chemotherapeutic, physiological properties and their dynamic nature has attracted the attention of chemist during last few years 1. Acting as versatile scaffolds, benzofuran derivatives can be used to synthesize potentially new therapeutic agents 2. These scaffolds exhibited biological properties such as antimicrobial 3 , analgesic 4 , anti-hyperglycemic 5 , anti-parasitic 6 , antitumor and kinase inhibitors 7. Besides these properties benzofuran scaffolds also found application as oxidant 8 , fluorescent sensor 9 , brightening agent, antioxidant and in other field of chemistry and agriculture 10. Urease is a metalloenzyme contain nickel that is responsible for catalyzing urea hydrolysis to ammonia and carbamate, the latter spontaneously hydrolyzing to carbonic acid and a second molecule of ammonia in an uncatalyzed reaction 11. Ammonia molecules thus formed are protonated by water at physiological pH, whereas the carbonic acid dissociates and causes an increase in pH.

Research paper thumbnail of In vivo anti-nociceptive potential and cyclooxygenases 1 and 2 selectivity of di-naphthodiospyrols from Diospyros lotus

Revista Brasileira de Farmacognosia

Research paper thumbnail of Aryl-oxadiazole Schiff bases: Synthesis, α-glucosidase in vitro inhibitory activity and their in silico studies

Arabian Journal of Chemistry

Research paper thumbnail of In Silico Modeling of Crimean Congo Hemorrhagic Fever Virus Glycoprotein-N and Screening of Anti Viral Hits by Virtual Screening

International Journal of Peptide Research and Therapeutics

Crimean-Congo hemorrhagic fever (CCHF) is a widespread zoonotic viral disease, caused by a tick-b... more Crimean-Congo hemorrhagic fever (CCHF) is a widespread zoonotic viral disease, caused by a tick-born virus Crimean-Congo hemorrhagic fever virus (CCHFV). This disease is endemic in Middle East, Asia, Africa and SouthEastern Europe with the mortality rate of 5-30%. CCHFV genome is composed of three segments: large, medium and small segments. M segment encodes a polyprotein (glycoprotein) so called glycoprotein N (Gn) which is considered as a potential druggable target for the effective therapy of CCHF. The complete structure of Gn is still not characterized. The aim of the current study is to predict the complete three-dimensional (3D-) structure of CCHFV Gn protein via threading-based modeling and investigate the residues crucial for binding with CCHFV envelop. The developed model displayed excellent stereo-chemical and geometrical properties. Subsequently structure based virtual screening (SBVS) was applied to discover novel inhibitors of Gn protein. A library of > 1300 anti-virals was selected from PubChem database and directed to the predicted binding site of Gn. The SBVS results led to the identification of thirty-seven compounds that inhibit the protein in computational analysis. Those 37 hits were subject to pharmacokinetic profiling which demonstrated that 30/37 compound possess safer pharmacokinetic properties. Thus, by specifically targeting Gn, less toxic and more potent inhibitors of CCHFV were identified in silico.

Research paper thumbnail of In-silico design of peptide inhibitors of K-Ras target in cancer disease

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of Theoretical and Experimental in vitro Antifungal and Antitumor Activities of Organotin(IV) Derivatives of 3-(4-nitrophenyl)-2-methylacrylic acid

Pharmaceutical Chemistry Journal

Research paper thumbnail of Synthesis, In vitro α-Amylase Inhibitory, and Radicals (DPPH ABTS) Scavenging Potentials of New N-Sulfonohydrazide Substituted Indazoles

Research paper thumbnail of Synthesis, in vitro urease inhibitory activity and molecular docking of 3,5‐disubstituted thiadiazine‐2‐thiones

Journal of Heterocyclic Chemistry

Research paper thumbnail of Synthesis of benzotriazoles derivatives and their dual potential as α-amylase and α-glucosidase inhibitors in vitro: Structure-activity relationship, molecular docking, and kinetic studies

European Journal of Medicinal Chemistry

Research paper thumbnail of Proteome-wide subtractive approach to prioritize a hypothetical protein of XDR-Mycobacterium tuberculosis as potential drug target

Genes & Genomics

Background Among the resistant isolates of MTB, multidrug resistant tuberculosis (MDR-TB) and ext... more Background Among the resistant isolates of MTB, multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) have been the areas of growing concern. The genomic analysis showed that the respective genomic pool of the XDR-MTB proteome contains more than 30% of the hypothetical proteins for which no functions have been annotated yet. This class of proteins presumably have their own importance to complete genome and proteome information. The bioinformatics advancements have helped to annotate those hypothetical proteins by using various computational tools and have potential to classify them functionally. Objective The objective of this study was to propose a new and unique drug target against the deadly Mycobacterium tuberculosis using Bioinformatics approaches to characterize the hypothetical proteins. Results We stepwise reduced the hypothetical proteins (total number: 1256) out of the complete proteome to only 26 essential hypothetical proteins. Out of those 26 proteins, the protein WP_003401246.1 was computationally characterized as the druggable target. Conclusion The study proposed a hypothetical protein from complete proteome of the XDR-MTB as a new drug target against which new drug candidates can be proposed. Hence, the study opens up the new avenues in the areas of drug discovery against deadly M. tuberculosis.

Research paper thumbnail of Synthesis, In vitro α-Glucosidase Inhibitory Potential and Molecular Docking Studies of 2-Amino-1,3,4-Oxadiazole Derivatives

Medicinal Chemistry

Background: In the recent past, we had synthesized and reported different derivatives of oxadiazo... more Background: In the recent past, we had synthesized and reported different derivatives of oxadiazoles as potential α-glucosidase inhibitors. Keeping in mind, the pharmacological aspects of oxadiazole moiety and in continuation of our ongoing research on the chemistry and bioactivity of new heterocyclic compounds. Method: 1,3,4-Oxadiazole derivatives (1-14) have been synthesized and characterized by different spectroscopic techniques such as 1H-, 13C-NMR and HREI-MS. Result: The synthetic derivatives were screened for α-glucosidase inhibitory potential, all compounds exhibited good inhibitory activity with IC50 values ranging between 0.80 ± 0.1 to 45.1 ± 1.7 μM in comparison with the standard acarbose having IC50 value 38.45 ± 0.80 μM. Conclusion: Thirteen compounds 1-6 and 8-14 showed potential inhibitory activity as compared to the standard acarbose having IC50 values 38.45 ± 0.80 μM, however, only one compound 7 (IC50 = 45.1 ± 1.7 μM) was found to be less active. Compound 14 (IC50 ...