Ritesh Bhole - Academia.edu (original) (raw)

Papers by Ritesh Bhole

PLOS ONE

The present study intends to formulate, characterize and appraise the phospholipid-based nanovesi... more The present study intends to formulate, characterize and appraise the phospholipid-based nanovesicular system for enhanced delivery of Hesperetin (HT). The quality by design (QbD) approach was employed to prepare Hesperetin naturosomes (HTN) using the solvent evaporation technique and assessed for physicochemical and pharmacological attributes. The FTIR, DSC, and PXRD studies confirmed the successful formation of a vesicular drug-phospholipid complex, while photomicroscopy, SEM, and TEM analysis revealed the morphology of HTN. The functional attributes substantially enhanced the HT’s aqueous solubility, drug release, and membrane permeation. The aqueous solubility of HTN was ~10-fold more than that of pure HT. Likewise, the in-vitro dissolution data of HTN showed better competence in releasing the HT (>93%) than the pure HT (~64%) or the physical mixture (~74%). Furthermore, HTN significantly altered HT permeation (>53%) when compared to pure HT (23%) or the physical mixture (...

Current Indian Science

Selenium is an essential trace element. It is, however toxic at concentration little above which ... more Selenium is an essential trace element. It is, however toxic at concentration little above which is required for health. Selenium is incorporated into proteins as selenocysteine, the 21(st) amino acid. Selenoproteins are found in bacteria, archaea and eukaryotes. Biochemical and physicochemical properties of selenium result in the unique redox characteristics of selenocysteine and its use in antioxidant enzymes. In this context of a redox reaction is the reduction of reactive oxygen metabolites by glutathione peroxidases, helping to maintain membrane integrity, reduces the oxidative damage to lipids, lipoproteins, and DNA. Selenium has structural and enzymatic roles. Selenium influences a number of endocrine processes, most notably, those involved in thyroid hormone synthesis and metabolism. Se is needed for the proper functioning of the immune system, a role in viral suppression, AIDS, and also is implicated in delaying the aging process. Its deficiency has been linked to a number of disorders such as heart disease, diabetes, and diseases of the liver, and it is required for sperm motility and may reduce the risk of miscarriage. Se supplementation has recently moved from the realm of correcting nutritional deficiencies to one of pharmacological intervention, especially in the clinical domain of cancer chemoprevention. During the last few years, a tremendous effort has been directed toward the synthesis of stable organoselenium compounds that could be used as antioxidants, enzyme modulators, antitumor, antimicrobials, antihypertensive agents, antivirals and cytokine inducers. The biochemistry and pharmacology of selenium-based compounds are subjects of intense current interest, especially from the point of view of public heath. The purpose of this review is to discuss the recent pharmacological applications of organoselenium compounds as therapeutic agents in the treatment of several diseases.

Turkish Journal of Oncology

Cancer is a group of diseases characterized by uncontrolled and abnormal cell growth, leading to ... more Cancer is a group of diseases characterized by uncontrolled and abnormal cell growth, leading to serious health consequences. Although various approaches are available for treating cancer, including chemotherapy, surgery, radiation, and immunotherapy, the severe adverse effects of these approaches limit their clinical effectiveness. New cancer treatment strategies including phototherapy uses light to treat cancer, which has attracted wide interest in the oncology research community. There are two types of phototherapy: photodynamic therapy (PDT) and phototherapy (PTT). PDT requires the administration of a photosensitizing agent and light exposure at a particular wavelength. On the other hand, PTT uses a photothermal agent that activates and kills cancer cells at a longer wavelength of light; hence, it is less energetic and, therefore, less harmful to other cells and tissues. PTT is gaining tremendous popularity because of its limited side-effects. A significant downside of PDT is that the photosensitizing drug stays in the body for a long time, which renders the patients extremely sensitive to light exposure. PDT is useful for the treatment of lining organs as they are can be easily reached by the light source. Although PDT is helpful for treating lining organs, its potential side-effects have been reported in the treatment of skin mouth esophagus and lung cancer, among others. Therefore, PTT remains a good alternative for cancer treatment.

Research and Reviews: A Journal of Pharmaceutical Science, Jun 19, 2019

Research and Reviews: A Journal of Pharmaceutical Science, Jul 11, 2019

Quantitative structure activity relationship; COX inhibitor; LOO model. ABSTRACT Selective COX-2 ... more Quantitative structure activity relationship; COX inhibitor; LOO model. ABSTRACT Selective COX-2 inhibitor have attracted much attention in recent times in design of non-steroidal anti-inflammatory agents(NSAID), which are devoid of the common side effects of classical NSAIDs. QSAR studies have been performed on a series of benzothiazolamines that acts as selective COX-2 inhibitor using a three dimensional QSAR. The studies were carried on twenty analogs. Various physicochemical parameter were calculated using Chem Office 2001 software.QSAR models were generated for cyclooxygenase inhibitor activity using stepwise multiple regression analysis. Statistically significant models were obtained gave r 2 value(square of correlation coefficient) as 0.8102 after per oral, 2h. The studies indicated that the anti-inflammatory activity is depend on spatial and thermodynamic descriptor. Cross validation was performed using the leave one out method. Obtained and validated models bring important ...

site av sheets P2 are featur and m tronic by A tronic purely NaxM were ductiv It h of A transp of... more site av sheets P2 are featur and m tronic by A tronic purely NaxM were ductiv It h of A transp of co when O) to Howe old ov

Heliyon, 2021

The androgen receptor inhibitor, Enzalutamide, proved effective against castration resistance pro... more The androgen receptor inhibitor, Enzalutamide, proved effective against castration resistance prostate cancer, has demonstrated clinical benefits and increased survival rate in men. However, AR mutation (F876L) converts Enzalutamide from antagonist to agonist indicating a rapid evolution of resistance. Hence, our goal is to overcome this resistance mechanism by designing and developing novel Enzalutamide analogues. We designed a dataset of Enzalutamide derivatives using Enzalutamide's shape and electrostatic features to match with pharmacophoric features essential for tight binding with the androgen receptor. Based on this design strategy ten novel derivatives were selected including 5,5-dimethyl-3-(6-substituted benzo[d]thia/oxazol-2-yl)-2-thioxo-1-(4-(trifluoromethyl) pyridin-2-yl)imidazolidin-4-one (6a-j) for synthesis. All the compounds were evaluated in-vitro on prostate cancer cell lines DU-145, LNCaP and PC3. Interestingly, two compounds 3-(6-hydroxybenzo[d]thiazol-2-yl)-5,5dimethyl-2-thioxo-1-(4-(trifluoromethyl)pyridin-2-yl) imidazolidin-4-one (6c, IC 50-18.26 to 20.31μM) and 3-(6hydroxybenzo[d]oxazol-2-yl)-5,5-dimethyl-2-thioxo-1-(4-(trifluoromethyl) pyridin-2-yl)imidazolidin-4-one (6h, IC 50-18.26 to 20.31μM) were successful with promising in-vitro antiproliferative activity against prostate cancer cell lines. The binding mechanism of potential androgen receptor inhibitors was further studied by molecular docking, molecular dynamics simulations and MM-GBSA binding free energy calculations and found in agreement with the in vitro studies. It provided strong theoretical support to our hypothesis.

The estimation of Terizidone in pharmaceutical dosage form by using High Performance Thin Layer C... more The estimation of Terizidone in pharmaceutical dosage form by using High Performance Thin Layer Chromatography was done using CAMAG HPTLC system. The separation was achieved using precoated silica gel 60 F 254 aluminium plates with mobile phase Toluene: n-Butanol 9:1 ml % v/v at wavelength 268 nm. The linearity range was found between 50-300 ng/ml-band having correlation coefficient 0.997. The recovery study of method showed the recovery between 99.3-101.6%. The LOD and LOQ values for method were 0.981 and 2.973 respectively. The R.S.D. of precision study was less than 2. The method parameters were validated as per ICH guidelines. The forced degradation studies revealed that the drug found stable in acidic, thermal and photo degradation. The LC-MS/MS study of degraded products gave the idea about the fragmentation patterns of degraded products.The developed method can be used for routine analysis of Terizidone and its formulations.

A simple, accurate and reproducible UV-Spectrophotometric and Stability indicating RP-HPLC method... more A simple, accurate and reproducible UV-Spectrophotometric and Stability indicating RP-HPLC methods have been developed for simultaneous estimation of Metoprolol Succinate and Hydrochlorothiazide in tablet..

Asian Journal of Research in Chemistry, 2008

A series of sulphonamide derivatives having benzothiazole nucleus have been synthesized by conden... more A series of sulphonamide derivatives having benzothiazole nucleus have been synthesized by condensation of 2-aminobenzothiazole with 4-acetamidobenzenesulphonyl chloride derivatives in pyridine-acetic anhydride mixture. The identity of the compounds 4-acetamido-N-(1, 3-benzothiazol-2-yl) benzene sulphonamide and 4-amino-N-(1,3-benzothiazol-2-yl)benzene-sulphonamide has been characterized by elemental analysis and spectral data. All the test compounds have been assayed in vitro for antibacterial activity against B. subtilis and E. coli, antifungal activity against C. albicans and the antimycobacterial activity against H37Rv strain of mycobacterium tuberculosis. The test compounds showed significant antibacterial, antifungal and antimycobacterial activity against the microbial strains used.

Jordan Journal of Pharmaceutical Sciences, 2019

Bladder cancer is one of the deadly cancer with 16,390 deaths in 2015-16 alone and 76,960 new cas... more Bladder cancer is one of the deadly cancer with 16,390 deaths in 2015-16 alone and 76,960 new cases. The matter of concern is more severe with very limited options of treatment and lack of new drugs, cisplatin and doxorubicin are the only two drugs mostly used in therapy. This situation along with the epidemiological data calls for development of newer better and safer agents. Herein, we report nine novel benzothiazole derivatives based on structure based drug discovery and molecular modelling approach. Newly designed compounds were synthesised following four step reaction and were characterized for structural confirmation. These novel compounds were evaluated on the MTT assay for there in vitro efficiency using the TCP1020 cell lines. These were further analysed for their mechanism of action based on in silico studies.Two compounds of the series exhibits promising results which are in agreement with the in silico studies. It was found that the methyl group at seventh position to th...

European review for medical and pharmacological sciences, 2020

The Coronavirus disease (COVID-19) caused by the novel SARS-CoV-2 coronavirus has spread from Chi... more The Coronavirus disease (COVID-19) caused by the novel SARS-CoV-2 coronavirus has spread from China and quickly transmitted to most other countries around the world. The World Health Organization announced COVID-19 as a pandemic that is spreading steadily and soon in most states. Coronavirus genomic characterization showed that it most closely resembled another bat-origin beta-coronavirus. Coronavirus has the largest genome of viruses that have RNA. Spike (S) glycoprotein is present in the virus and is responsible for virus entry into the host cell. COVID-19 can spread through the droplet, direct contact, and aerosol transmission in humans. It can remain in the environment and exists on plastic and steel for the longest time, making it a dangerous and contagious disease that can kill other individuals. The virus has an incubation time of 2 to 14 days. Confirmed cases of COVID-19 have evolved exponentially in the world. Possible preventive steps for disease control include more mask ...

Attempts were made to perform comparative docking study of Aloe emodin and its derivative on Nepr... more Attempts were made to perform comparative docking study of Aloe emodin and its derivative on Neprilysin (PDB code: 1R1J) by using VLife MDS software to ascertain the activity of both. From all the interactions (Hydrogen bond and vander waals) it was observed that, the common amino acids which interacts with the common ligand were ASN542A, ALA543A, ARG102A, ASN542A, VAL580A. The result showed that the AEC ( –1790.15 KCal ) showed high total binding energy ( ΔG ) as compared to AE (–1289.55 KCal ). Interactions of AEC reference ligand with protein NEP were studied. The results revels high vander wall bond interaction compared to hydrogen bond among different amino acid. The compound may be the most active anti-aging agent as per Docking results. The compound AEC was most active while compound AE was least active as per docking. Keywords: Docking, antiaging, Aloe emodin, Neprilysin

To develop potent anticancer compounds using benzothiazole scaffolds GQSAR analysis was performed... more To develop potent anticancer compounds using benzothiazole scaffolds GQSAR analysis was performed on 41 reported benzothiazole derivatives for identification of structural fragments. Benzothiazole dataset was fragmented in to two fragments (R1 and R2). GQSAR models were generated using MLR. GQSAR analysis revealed presence of hydrophobic groups on R1 will potentiate anticancer activity. The generated models are giving insight into the benzothiazole structural requirements which will be optimized for design of anticancer drugs.

Bulletin of the Karaganda University. "Chemistry" series, 2021

Cancer is a chronic disease which can cause death. In traditional chemotherapycytotoxic drugs are... more Cancer is a chronic disease which can cause death. In traditional chemotherapycytotoxic drugs are used to kill proliferating cancer cells. The cytotoxic agent exhibits less specificity, less biological activity, causes sys-temic toxicity and undesirable side effects. Each year, about 1.8 million of the population are infected and die due to tuberculosis infection. An increase of drug resistance during the tuberculosis treatment is a significant concern. So, it is necessary to develop a new approach or therapies to resolve drug resistance, drug selectivity in tuberculosis infection and the reduction of the side effects of cytotoxic agents and anti-tubercular drugs. This review describes the newly emerging concept of «vitamin drug conjugate». Vitamin-drug conjugate is a specifically carried drug toward the target site, is one of the promising ways to treat chronic diseases like can-cer and tuberculosis and enhance the therapeutic outcome. The purpose of this review is to explore vitam...

Journal of Molecular Structure, 2022

Abstract Adenosine Triphosphate synthase (ATPs) is an important enzyme for the synthesis of adeno... more Abstract Adenosine Triphosphate synthase (ATPs) is an important enzyme for the synthesis of adenosine triphosphate (ATP). ATP is principal source of energy for growth and development of mycobacteria. ATPs is a validated drug target for discovery of new anti-TB drug against drug resistant bacterial strain. Since then, inhibitor with different type of chemical scaffolds have been reported for their activity against this enzyme. Formation of polar and non-polar interaction by ligand with this enzyme causes loss of catalytic activity which ultimately lead to death of mycobacterium. This review describes various ATPs inhibitors, their biological activity, and Structure Activity Relationship (SAR) reported in various literature up to date. We look beyond for the search of newer ATPs inhibitor or combination therapies to tackle drug resistant tuberculosis.

Journal of Drug Delivery Science and Technology, 2021

Abstract In dosage form design, drug delivery technology facing a major problem due to degradatio... more Abstract In dosage form design, drug delivery technology facing a major problem due to degradation of the drug through the first-pass metabolism upon oral delivery. We can overcome this bioavailability-related problem by adopting the intestinal lymphatic pathway for drug delivery. Nanocarriers like lipid nanoparticles, polymeric nanoparticles, liposomes, emulsions, etc. can be used to enhance the lymphatic uptake of drugs. In the lymphatic pathway absorption of drugs takes place by endocytosis via Peyer's patches and the chylomicron uptake. Peyer's patches exhibit M-cells which represent many receptors like mannose receptors, folate receptors, claudins, integrins, transferrin receptors, biotin receptors etc. Targeting these receptors through nanocarriers can improve the lymphatic absorption of drugs and thus improve bioavailability. Targeting drugs through the lymphatic system can treat many diseases including cancer, AIDS, tuberculosis, lymphodema, diabetes, schizophrenia, etc. Thus, by using lymphatic drug delivery systems we can improve the treatment efficacy, survival, and life expectancy of the patient. In this article, we discussed various strategies to enhance drug bioavailability through lymphatic targeting.

Bulletin of the Karaganda University. "Chemistry" series, 2021

Cancer is the uncontrolled growth of cells in the human body that has the ability to spread. The ... more Cancer is the uncontrolled growth of cells in the human body that has the ability to spread. The purpose of the study is to explore that vitamins can be used as a targeting moiety for new anticancer drugs to address issues like non-selectivity, systemic toxicity. 5-Fluorouracil acetic acid–Vitamin D3 (5FUAC-Vit.D3) conjugate has been synthesized, characterized, and evaluated for its anticancer activity. 5-FUAC-Vit.D3 conjugate was synthesized via esterification mechanism in the presence of N-Hydroxy succinimide (NHS) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (EDC) by using HCL as coupling agent. Formation of 5-FUAC-Vit.D3 conjugate via esteric bond and the structure of the compounds were confirmed by spectroscopic data, i.e., IR, NMR, and mass spectra. The docking studies showed that 5-FUAC-Vit.D3 conjugate interacted at Arg-215 and Lys-47 of the human thymidylate synthase proteins, through hydrogen bonding and ionic bonds respectively with a binding score of -8.614 which is...

Bioorganic Chemistry, 2021

Enoyl acyl carrier protein reductase (InhA) is a key enzyme involved in fatty acid synthesis main... more Enoyl acyl carrier protein reductase (InhA) is a key enzyme involved in fatty acid synthesis mainly mycolic acid biosynthesis that is a part of NADH dependent acyl carrier protein reductase family. The aim of the present literature is to underline the different scaffolds or enzyme inhibitors that inhibit mycolic acid biosynthesis mainly cell wall synthesis by inhibiting enzyme InhA. Various scaffolds were identified based on the screening technologies like high throughput screening, encoded library technology, fragment-based screening. The compounds studied include indirect inhibitors (Isoniazid, Ethionamide, Prothionamide) and direct inhibitors (Triclosan/Diphenyl ethers, Pyrrolidine Carboxamides, Pyrroles, Acetamides, Thiadiazoles, Triazoles) with better efficacy against drug resistance. Out of the several scaffolds studied, pyrrolidine carboxamides were found to be the best molecules targeting InhA having good bioavailability properties and better MIC. This review provides with a detailed information, analysis, structure activity relationship and useful insight on various scaffolds as InhA inhibitors.

PLOS ONE

The present study intends to formulate, characterize and appraise the phospholipid-based nanovesi... more The present study intends to formulate, characterize and appraise the phospholipid-based nanovesicular system for enhanced delivery of Hesperetin (HT). The quality by design (QbD) approach was employed to prepare Hesperetin naturosomes (HTN) using the solvent evaporation technique and assessed for physicochemical and pharmacological attributes. The FTIR, DSC, and PXRD studies confirmed the successful formation of a vesicular drug-phospholipid complex, while photomicroscopy, SEM, and TEM analysis revealed the morphology of HTN. The functional attributes substantially enhanced the HT’s aqueous solubility, drug release, and membrane permeation. The aqueous solubility of HTN was ~10-fold more than that of pure HT. Likewise, the in-vitro dissolution data of HTN showed better competence in releasing the HT (>93%) than the pure HT (~64%) or the physical mixture (~74%). Furthermore, HTN significantly altered HT permeation (>53%) when compared to pure HT (23%) or the physical mixture (...

Current Indian Science

Selenium is an essential trace element. It is, however toxic at concentration little above which ... more Selenium is an essential trace element. It is, however toxic at concentration little above which is required for health. Selenium is incorporated into proteins as selenocysteine, the 21(st) amino acid. Selenoproteins are found in bacteria, archaea and eukaryotes. Biochemical and physicochemical properties of selenium result in the unique redox characteristics of selenocysteine and its use in antioxidant enzymes. In this context of a redox reaction is the reduction of reactive oxygen metabolites by glutathione peroxidases, helping to maintain membrane integrity, reduces the oxidative damage to lipids, lipoproteins, and DNA. Selenium has structural and enzymatic roles. Selenium influences a number of endocrine processes, most notably, those involved in thyroid hormone synthesis and metabolism. Se is needed for the proper functioning of the immune system, a role in viral suppression, AIDS, and also is implicated in delaying the aging process. Its deficiency has been linked to a number of disorders such as heart disease, diabetes, and diseases of the liver, and it is required for sperm motility and may reduce the risk of miscarriage. Se supplementation has recently moved from the realm of correcting nutritional deficiencies to one of pharmacological intervention, especially in the clinical domain of cancer chemoprevention. During the last few years, a tremendous effort has been directed toward the synthesis of stable organoselenium compounds that could be used as antioxidants, enzyme modulators, antitumor, antimicrobials, antihypertensive agents, antivirals and cytokine inducers. The biochemistry and pharmacology of selenium-based compounds are subjects of intense current interest, especially from the point of view of public heath. The purpose of this review is to discuss the recent pharmacological applications of organoselenium compounds as therapeutic agents in the treatment of several diseases.

Turkish Journal of Oncology

Cancer is a group of diseases characterized by uncontrolled and abnormal cell growth, leading to ... more Cancer is a group of diseases characterized by uncontrolled and abnormal cell growth, leading to serious health consequences. Although various approaches are available for treating cancer, including chemotherapy, surgery, radiation, and immunotherapy, the severe adverse effects of these approaches limit their clinical effectiveness. New cancer treatment strategies including phototherapy uses light to treat cancer, which has attracted wide interest in the oncology research community. There are two types of phototherapy: photodynamic therapy (PDT) and phototherapy (PTT). PDT requires the administration of a photosensitizing agent and light exposure at a particular wavelength. On the other hand, PTT uses a photothermal agent that activates and kills cancer cells at a longer wavelength of light; hence, it is less energetic and, therefore, less harmful to other cells and tissues. PTT is gaining tremendous popularity because of its limited side-effects. A significant downside of PDT is that the photosensitizing drug stays in the body for a long time, which renders the patients extremely sensitive to light exposure. PDT is useful for the treatment of lining organs as they are can be easily reached by the light source. Although PDT is helpful for treating lining organs, its potential side-effects have been reported in the treatment of skin mouth esophagus and lung cancer, among others. Therefore, PTT remains a good alternative for cancer treatment.

Research and Reviews: A Journal of Pharmaceutical Science, Jun 19, 2019

Research and Reviews: A Journal of Pharmaceutical Science, Jul 11, 2019

Quantitative structure activity relationship; COX inhibitor; LOO model. ABSTRACT Selective COX-2 ... more Quantitative structure activity relationship; COX inhibitor; LOO model. ABSTRACT Selective COX-2 inhibitor have attracted much attention in recent times in design of non-steroidal anti-inflammatory agents(NSAID), which are devoid of the common side effects of classical NSAIDs. QSAR studies have been performed on a series of benzothiazolamines that acts as selective COX-2 inhibitor using a three dimensional QSAR. The studies were carried on twenty analogs. Various physicochemical parameter were calculated using Chem Office 2001 software.QSAR models were generated for cyclooxygenase inhibitor activity using stepwise multiple regression analysis. Statistically significant models were obtained gave r 2 value(square of correlation coefficient) as 0.8102 after per oral, 2h. The studies indicated that the anti-inflammatory activity is depend on spatial and thermodynamic descriptor. Cross validation was performed using the leave one out method. Obtained and validated models bring important ...

site av sheets P2 are featur and m tronic by A tronic purely NaxM were ductiv It h of A transp of... more site av sheets P2 are featur and m tronic by A tronic purely NaxM were ductiv It h of A transp of co when O) to Howe old ov

Heliyon, 2021

The androgen receptor inhibitor, Enzalutamide, proved effective against castration resistance pro... more The androgen receptor inhibitor, Enzalutamide, proved effective against castration resistance prostate cancer, has demonstrated clinical benefits and increased survival rate in men. However, AR mutation (F876L) converts Enzalutamide from antagonist to agonist indicating a rapid evolution of resistance. Hence, our goal is to overcome this resistance mechanism by designing and developing novel Enzalutamide analogues. We designed a dataset of Enzalutamide derivatives using Enzalutamide's shape and electrostatic features to match with pharmacophoric features essential for tight binding with the androgen receptor. Based on this design strategy ten novel derivatives were selected including 5,5-dimethyl-3-(6-substituted benzo[d]thia/oxazol-2-yl)-2-thioxo-1-(4-(trifluoromethyl) pyridin-2-yl)imidazolidin-4-one (6a-j) for synthesis. All the compounds were evaluated in-vitro on prostate cancer cell lines DU-145, LNCaP and PC3. Interestingly, two compounds 3-(6-hydroxybenzo[d]thiazol-2-yl)-5,5dimethyl-2-thioxo-1-(4-(trifluoromethyl)pyridin-2-yl) imidazolidin-4-one (6c, IC 50-18.26 to 20.31μM) and 3-(6hydroxybenzo[d]oxazol-2-yl)-5,5-dimethyl-2-thioxo-1-(4-(trifluoromethyl) pyridin-2-yl)imidazolidin-4-one (6h, IC 50-18.26 to 20.31μM) were successful with promising in-vitro antiproliferative activity against prostate cancer cell lines. The binding mechanism of potential androgen receptor inhibitors was further studied by molecular docking, molecular dynamics simulations and MM-GBSA binding free energy calculations and found in agreement with the in vitro studies. It provided strong theoretical support to our hypothesis.

The estimation of Terizidone in pharmaceutical dosage form by using High Performance Thin Layer C... more The estimation of Terizidone in pharmaceutical dosage form by using High Performance Thin Layer Chromatography was done using CAMAG HPTLC system. The separation was achieved using precoated silica gel 60 F 254 aluminium plates with mobile phase Toluene: n-Butanol 9:1 ml % v/v at wavelength 268 nm. The linearity range was found between 50-300 ng/ml-band having correlation coefficient 0.997. The recovery study of method showed the recovery between 99.3-101.6%. The LOD and LOQ values for method were 0.981 and 2.973 respectively. The R.S.D. of precision study was less than 2. The method parameters were validated as per ICH guidelines. The forced degradation studies revealed that the drug found stable in acidic, thermal and photo degradation. The LC-MS/MS study of degraded products gave the idea about the fragmentation patterns of degraded products.The developed method can be used for routine analysis of Terizidone and its formulations.

A simple, accurate and reproducible UV-Spectrophotometric and Stability indicating RP-HPLC method... more A simple, accurate and reproducible UV-Spectrophotometric and Stability indicating RP-HPLC methods have been developed for simultaneous estimation of Metoprolol Succinate and Hydrochlorothiazide in tablet..

Asian Journal of Research in Chemistry, 2008

A series of sulphonamide derivatives having benzothiazole nucleus have been synthesized by conden... more A series of sulphonamide derivatives having benzothiazole nucleus have been synthesized by condensation of 2-aminobenzothiazole with 4-acetamidobenzenesulphonyl chloride derivatives in pyridine-acetic anhydride mixture. The identity of the compounds 4-acetamido-N-(1, 3-benzothiazol-2-yl) benzene sulphonamide and 4-amino-N-(1,3-benzothiazol-2-yl)benzene-sulphonamide has been characterized by elemental analysis and spectral data. All the test compounds have been assayed in vitro for antibacterial activity against B. subtilis and E. coli, antifungal activity against C. albicans and the antimycobacterial activity against H37Rv strain of mycobacterium tuberculosis. The test compounds showed significant antibacterial, antifungal and antimycobacterial activity against the microbial strains used.

Jordan Journal of Pharmaceutical Sciences, 2019

Bladder cancer is one of the deadly cancer with 16,390 deaths in 2015-16 alone and 76,960 new cas... more Bladder cancer is one of the deadly cancer with 16,390 deaths in 2015-16 alone and 76,960 new cases. The matter of concern is more severe with very limited options of treatment and lack of new drugs, cisplatin and doxorubicin are the only two drugs mostly used in therapy. This situation along with the epidemiological data calls for development of newer better and safer agents. Herein, we report nine novel benzothiazole derivatives based on structure based drug discovery and molecular modelling approach. Newly designed compounds were synthesised following four step reaction and were characterized for structural confirmation. These novel compounds were evaluated on the MTT assay for there in vitro efficiency using the TCP1020 cell lines. These were further analysed for their mechanism of action based on in silico studies.Two compounds of the series exhibits promising results which are in agreement with the in silico studies. It was found that the methyl group at seventh position to th...

European review for medical and pharmacological sciences, 2020

The Coronavirus disease (COVID-19) caused by the novel SARS-CoV-2 coronavirus has spread from Chi... more The Coronavirus disease (COVID-19) caused by the novel SARS-CoV-2 coronavirus has spread from China and quickly transmitted to most other countries around the world. The World Health Organization announced COVID-19 as a pandemic that is spreading steadily and soon in most states. Coronavirus genomic characterization showed that it most closely resembled another bat-origin beta-coronavirus. Coronavirus has the largest genome of viruses that have RNA. Spike (S) glycoprotein is present in the virus and is responsible for virus entry into the host cell. COVID-19 can spread through the droplet, direct contact, and aerosol transmission in humans. It can remain in the environment and exists on plastic and steel for the longest time, making it a dangerous and contagious disease that can kill other individuals. The virus has an incubation time of 2 to 14 days. Confirmed cases of COVID-19 have evolved exponentially in the world. Possible preventive steps for disease control include more mask ...

Attempts were made to perform comparative docking study of Aloe emodin and its derivative on Nepr... more Attempts were made to perform comparative docking study of Aloe emodin and its derivative on Neprilysin (PDB code: 1R1J) by using VLife MDS software to ascertain the activity of both. From all the interactions (Hydrogen bond and vander waals) it was observed that, the common amino acids which interacts with the common ligand were ASN542A, ALA543A, ARG102A, ASN542A, VAL580A. The result showed that the AEC ( –1790.15 KCal ) showed high total binding energy ( ΔG ) as compared to AE (–1289.55 KCal ). Interactions of AEC reference ligand with protein NEP were studied. The results revels high vander wall bond interaction compared to hydrogen bond among different amino acid. The compound may be the most active anti-aging agent as per Docking results. The compound AEC was most active while compound AE was least active as per docking. Keywords: Docking, antiaging, Aloe emodin, Neprilysin

To develop potent anticancer compounds using benzothiazole scaffolds GQSAR analysis was performed... more To develop potent anticancer compounds using benzothiazole scaffolds GQSAR analysis was performed on 41 reported benzothiazole derivatives for identification of structural fragments. Benzothiazole dataset was fragmented in to two fragments (R1 and R2). GQSAR models were generated using MLR. GQSAR analysis revealed presence of hydrophobic groups on R1 will potentiate anticancer activity. The generated models are giving insight into the benzothiazole structural requirements which will be optimized for design of anticancer drugs.

Bulletin of the Karaganda University. "Chemistry" series, 2021

Cancer is a chronic disease which can cause death. In traditional chemotherapycytotoxic drugs are... more Cancer is a chronic disease which can cause death. In traditional chemotherapycytotoxic drugs are used to kill proliferating cancer cells. The cytotoxic agent exhibits less specificity, less biological activity, causes sys-temic toxicity and undesirable side effects. Each year, about 1.8 million of the population are infected and die due to tuberculosis infection. An increase of drug resistance during the tuberculosis treatment is a significant concern. So, it is necessary to develop a new approach or therapies to resolve drug resistance, drug selectivity in tuberculosis infection and the reduction of the side effects of cytotoxic agents and anti-tubercular drugs. This review describes the newly emerging concept of «vitamin drug conjugate». Vitamin-drug conjugate is a specifically carried drug toward the target site, is one of the promising ways to treat chronic diseases like can-cer and tuberculosis and enhance the therapeutic outcome. The purpose of this review is to explore vitam...

Journal of Molecular Structure, 2022

Abstract Adenosine Triphosphate synthase (ATPs) is an important enzyme for the synthesis of adeno... more Abstract Adenosine Triphosphate synthase (ATPs) is an important enzyme for the synthesis of adenosine triphosphate (ATP). ATP is principal source of energy for growth and development of mycobacteria. ATPs is a validated drug target for discovery of new anti-TB drug against drug resistant bacterial strain. Since then, inhibitor with different type of chemical scaffolds have been reported for their activity against this enzyme. Formation of polar and non-polar interaction by ligand with this enzyme causes loss of catalytic activity which ultimately lead to death of mycobacterium. This review describes various ATPs inhibitors, their biological activity, and Structure Activity Relationship (SAR) reported in various literature up to date. We look beyond for the search of newer ATPs inhibitor or combination therapies to tackle drug resistant tuberculosis.

Journal of Drug Delivery Science and Technology, 2021

Abstract In dosage form design, drug delivery technology facing a major problem due to degradatio... more Abstract In dosage form design, drug delivery technology facing a major problem due to degradation of the drug through the first-pass metabolism upon oral delivery. We can overcome this bioavailability-related problem by adopting the intestinal lymphatic pathway for drug delivery. Nanocarriers like lipid nanoparticles, polymeric nanoparticles, liposomes, emulsions, etc. can be used to enhance the lymphatic uptake of drugs. In the lymphatic pathway absorption of drugs takes place by endocytosis via Peyer's patches and the chylomicron uptake. Peyer's patches exhibit M-cells which represent many receptors like mannose receptors, folate receptors, claudins, integrins, transferrin receptors, biotin receptors etc. Targeting these receptors through nanocarriers can improve the lymphatic absorption of drugs and thus improve bioavailability. Targeting drugs through the lymphatic system can treat many diseases including cancer, AIDS, tuberculosis, lymphodema, diabetes, schizophrenia, etc. Thus, by using lymphatic drug delivery systems we can improve the treatment efficacy, survival, and life expectancy of the patient. In this article, we discussed various strategies to enhance drug bioavailability through lymphatic targeting.

Bulletin of the Karaganda University. "Chemistry" series, 2021

Cancer is the uncontrolled growth of cells in the human body that has the ability to spread. The ... more Cancer is the uncontrolled growth of cells in the human body that has the ability to spread. The purpose of the study is to explore that vitamins can be used as a targeting moiety for new anticancer drugs to address issues like non-selectivity, systemic toxicity. 5-Fluorouracil acetic acid–Vitamin D3 (5FUAC-Vit.D3) conjugate has been synthesized, characterized, and evaluated for its anticancer activity. 5-FUAC-Vit.D3 conjugate was synthesized via esterification mechanism in the presence of N-Hydroxy succinimide (NHS) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (EDC) by using HCL as coupling agent. Formation of 5-FUAC-Vit.D3 conjugate via esteric bond and the structure of the compounds were confirmed by spectroscopic data, i.e., IR, NMR, and mass spectra. The docking studies showed that 5-FUAC-Vit.D3 conjugate interacted at Arg-215 and Lys-47 of the human thymidylate synthase proteins, through hydrogen bonding and ionic bonds respectively with a binding score of -8.614 which is...

Bioorganic Chemistry, 2021

Enoyl acyl carrier protein reductase (InhA) is a key enzyme involved in fatty acid synthesis main... more Enoyl acyl carrier protein reductase (InhA) is a key enzyme involved in fatty acid synthesis mainly mycolic acid biosynthesis that is a part of NADH dependent acyl carrier protein reductase family. The aim of the present literature is to underline the different scaffolds or enzyme inhibitors that inhibit mycolic acid biosynthesis mainly cell wall synthesis by inhibiting enzyme InhA. Various scaffolds were identified based on the screening technologies like high throughput screening, encoded library technology, fragment-based screening. The compounds studied include indirect inhibitors (Isoniazid, Ethionamide, Prothionamide) and direct inhibitors (Triclosan/Diphenyl ethers, Pyrrolidine Carboxamides, Pyrroles, Acetamides, Thiadiazoles, Triazoles) with better efficacy against drug resistance. Out of the several scaffolds studied, pyrrolidine carboxamides were found to be the best molecules targeting InhA having good bioavailability properties and better MIC. This review provides with a detailed information, analysis, structure activity relationship and useful insight on various scaffolds as InhA inhibitors.