Papers by Shashikant Dhawale
International Journal of Botany Studies, 2021
IntechOpen eBooks, May 4, 2021
Momordica charantia L. is growing in many tropical and subtropical regions; the fruits of bitter ... more Momordica charantia L. is growing in many tropical and subtropical regions; the fruits of bitter melon are also gradually becoming popular for treating diabetes and associated diseases. Over 248 compounds belonging to the lipids, phenolics and terpenoids class are reported by diverse studies. However, M. charantia L. appears to be an inimitable species that synthesizes a diverse range of natural products in the fruits, leaves, stems and roots. The cucurbitane types of triterpenes exist in the various tissues of the plant in their aglycone as well as glycosylated forms. The bitter melon seems to exert their lipid lowering and antiobesity effects via several mechanisms like PPARs, LXRs, SREBPs, and Sirts mediated fat metabolism in various tissues, prevent adipocyte hypertrophy and visceral fat accumulation. M. charantia L. has been comprehensively studied worldwide for its therapeutic properties to treat a number of diseases like diabetes, dyslipidaemia, obesity, and certain cancers. This chapter apparently displays an encompassing literature review on vast potential of bitter melon as antiobesity agent and assembles data on complex phytochemistry.
A novel series of N 1-(substituted pyridine-2-yl)-N 3-(quinoline-2-yl) malonamide derivatives (AK... more A novel series of N 1-(substituted pyridine-2-yl)-N 3-(quinoline-2-yl) malonamide derivatives (AK 1-AK 24) has been rationally designed, synthesized and biologically screened for in vitro anti HIV activity by using reverse transcriptase assay kit (Roche). Out of the synthesized compounds, compound AK 1 , AK 2 and AK 3 show potent reverse transcriptase (RT) inhibitor activity and compounds AK 4 to AK 9 , AK 11 , AK 12, AK 13 and AK 14 show RT inhibitory activity comparable with standard rilpivirine. In docking studies, those compounds show higher G-Score which indicates higher percentage of inhibition of reverse transcriptase during in vitro screening. In silico pharmacokinetic studies imply that synthesized derivatives have no CYP450 inhibition, no BBB penetration and good oral absorption. Virtual toxicity studies performed by using Toxtree-v 2.6.6 in various computational animal models show high LD50 values and the compounds are found to be non-carcinogenic.
Der Pharmacia Lettre, 2016
Antitubercular drug discovery is a challenging strain in the recent era. Quinazolines are an impo... more Antitubercular drug discovery is a challenging strain in the recent era. Quinazolines are an important chemical compounds having diverse significant biological activities. Three dimensional Quantitative structure-activity relationships (3D QSAR) represent an attempt to correlate three dimensional structural features of compounds with biological activities. The pharmacophore identification and QSAR studies on C-2 and C-4 substituted quinazoline series was carried out by partial least-squares (PLS) method to identify the potential framework of the molecules responsible for the antitubercular activity. The QSAR models were developed considering training and test set approaches further validated for statistical significance and predictive ability by internal and external validation. The results of 3D QSAR model demonstrate the high degree of statistical importance and excellent predictive capability. The hydrogen bond accepter, hydrogen bond donor, positively charged, aromatic carbon, steric and hydrophobic parameter are the important features contributing towards the activity. The selected best QSAR model A has a training set of 20 molecules and test set of 6 molecules with correction coefficient of 0.9641.
Indian Journal of Pharmaceutical Sciences, 2022
Medicinal plants have recently gained popularity and are now commonly used to treat a variety of ... more Medicinal plants have recently gained popularity and are now commonly used to treat a variety of diseases. The aim of this research was to evaluate antioxidant and anti-lipase activities of two commonly used medicinal plants in vitro. The solvents like chloroform, acetone and 70 % ethanol were used to extract the dried leaves of Momordica charantia and Psoralea corylifolia. Folin-Ciocateu's reagent and the aluminum chloride colorimetry process were used to determine the total phenolic and flavonoid contents, respectively. Further the extracts were screened for in vitro antioxidant activity, analyzed by 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power assay. Using pancreatic lipase enzyme inhibition, the anti-lipase potential of extracts was studied and compared to that of the reference drug orlistat. The phytochemical analysis revealed that the ethanol extract of Momordica charantia had the highest total phenolic and total flavonoid content (89.96±0.29 mg gallic acid equivalents/g of dry extract; 82.55±0.03 mg quercetin equivalents/g of dry extract, respectively) of all the plant extracts examined. The ethanol extract of Momordica charantia exhibited substantial radical scavenging and ferric reducing potential, with IC 50 values of 96.85±0.04 μg/ml and 99.43±0.06 μg/ml, respectively. Anti-lipase activity was found in all of the extracts. The ethanol extract of Momordica charantia, on the other hand, demonstrated strong anti-lipase activity, with an IC 50 value of 27.70±0.15 μg/ml (p< 0.01). The standard drug orlistat (18.15±0.34 μg/ml) showed the greatest anti-lipase activity. Overall, Momordica charantia leaf extracts exhibited greater antioxidant and anti-lipase activity than Psoralea corylifolia. Momordica charantia and Psoralea corylifolia were found to be powerful antioxidants and pancreatic lipase inhibitors. A daily supplement of these plants, according to our findings, can aid in the reduction of obesity.
Journal of biologically active products from nature, Sep 3, 2015
Abstract A large population of immune compromised people is susceptible to opportunistic mycoses.... more Abstract A large population of immune compromised people is susceptible to opportunistic mycoses. Infections caused by Candida species, particularly Candida albicans, is a major cause of morbidity and mortality among the patients. Biofilm related infections of C. albicans pose a challenge to successful antifungal treatment because of their resistance to available drugs. Plants and plant derived products represent a rich platform for the discovery of pharmaceutically important molecules. The study evaluated activity of methanol and petroleum ether extracts of fruits of Helicteres isora Linn. against planktonic and biofilm growth of Candida albicans. Methanol extract of H. isora L. (MEHI) showed complete prevention of planktonic growth at 2 mg/ml, while petroleum ether extract (PEEHI) had no effect up to 4 mg/ml concentration. Decrease in biofilm formation was analyzed in presence of 1 mg/ml MEHI, and 2 mg/ml concentration of it prevented biofilm formation significantly (p< 0.05). In comparison, PEEHI exhibited negligible activity against biofilm. Results demonstrate anti-biofilm activity of methanol extract of H. isora L. fruit, in C. albicans.
A novel series of substituted 2-Amino-4,6-diarylpyrimidines (DAPY's)as Non-nucleoside reverse tra... more A novel series of substituted 2-Amino-4,6-diarylpyrimidines (DAPY's)as Non-nucleoside reverse transcriptase inhibitors (NNRTIs) were designed, synthesized and evaluated for in vitro reverse transcriptase (RT) inhibition activity. Out of the reported compounds, 4a, 4i, 4j and 4n showed potent anti-HIV activity as compared to standard rilpivirine. The other compounds displayed moderate activity against HIV-1. Binding affinities of the designed NCEs were studied on reverse transcriptase enzyme using docking studies and showed possible horseshoe conformation as required for the DAPY category of RT inhibitors. A correlation was found between the anti-HIV activity and the electrostatic energy interaction with Lys 101 residue.
Asian Journal of Pharmaceutical and Clinical Research, 2018
Objective: The purpose of the present investigation was to develop a nanosuspension to improve d... more Objective: The purpose of the present investigation was to develop a nanosuspension to improve dissolution rate and oral bioavailability of ritonavir.Methods: Extended-release ritonavir loaded nanoparticles were prepared using the polymeric system by nanoprecipitation technique. Further, the effect of Eudragit RL100 (polymeric matrix) and polyvinyl alcohol (surfactant) was investigated on particle size and distribution, drug content, entrapment efficiency, and in vitro drug release from nanosuspension where a strong influence of polymeric contents was observed. Drug-excipient compatibility and amorphous nature of drug in prepared nanoparticles were confirmed by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction studies, respectively.Results: Hydrophobic portions of Eudragit RL100 could result in enhanced encapsulation efficiency. However, increase in polymer and surfactant contents lead to enlarged particle size proportionately ...
Indian Drugs
It has been established that sulfoxide with sulfones have distinct pharmacological effects. Commo... more It has been established that sulfoxide with sulfones have distinct pharmacological effects. Commodity compounds like sulfoxide and sulfones find widespread use in many chemical disciplines. This is why organic chemists find the synthesis of sulfoxide and sulfones so interesting. In the process of oxidation, sulphides can transform into sulfoxides or sulfones. Comprehensive oxidation to the sulfones is significantly simpler than mild oxidation to the sulfoxide, but both can be achieved by the use of highly selective technologies.
Research Journal of Pharmacy and Technology, 2019
Hacettepe University Journal of the Faculty of Pharmacy
Momordica charantia L. (Bitter melon) has been used to treat hyperglycemia and hyperlipidemia in ... more Momordica charantia L. (Bitter melon) has been used to treat hyperglycemia and hyperlipidemia in many parts of the world. The present study revealed antihyperlipidemic activity of ethanolic leaf extract of M. charantia L. (named as EMC). The ethanolic extract of leaves was prepared and phytochemical constituents were identified using liquid chromatography linked with mass spectrophotometry. LC-HRMS study indicates the presence of phenolic compound (m-hydroxy benzoic acid, octyl gallate, 3-hydroxycoumarin), triterpenoids (momordicin II, momordicoside E and momordicoside K), saponin E and fatty acids were the major constituents in EMC. Whereas, Triton X-100 induced hyperlipidemic rat model was used to evaluate antihyperlipidemic activity of EMC at a dose of 50, 100 and 200 mg/kg, b.w. or atorvastatin (10 mg/kg, b.w.). The plasma total cholesterol, triglycerides, HDL, LDL and VLDL level, hepatic cholesterol and triglyceride, fecal cholesterol and triglycerides level were checked. Triton X-100 significantly (P < 0.01) increased the serum total cholesterol, triglycerides and LDL with a concomitant reduction in HDL cholesterol. These alterations were ameliorated by EMC at dose dependant manner. EMC (200 mg/kg, b.w) showed significant (P < 0.01) reduction in lipid level among three doses of extracts in comparison with the standard drug atorvastatin. Overall results findings suggest that bitter melon may have potential to use as supplementary ingredient for the prevention of hyperlipidemia and related conditions.
Future Journal of Pharmaceutical Sciences, 2021
Background Most of the edible portions like peel and skin of some fruits is discarded while consu... more Background Most of the edible portions like peel and skin of some fruits is discarded while consuming it, though they are rich in several health beneficial phytochemicals or nutrients. Many reports from literature are about fruit pulp of (Sapota) Manilkara zapota (L) P. Royen having high radical scavenging and antioxidant potential, but the studies relating to peel extracts are scanty. Regardless of its commendable phytoconstituents which could have free radical scavenging potential, this fruit peel is as yet still needed to be assessed for in vitro antidiabetic prospects. Hence, the present study aims at evaluating in vitro free radical scavenging and α-glucosidase enzyme hindrance abilities of this fruit peel. Results With a maximum considerable % extractive yield (18.90%) in 70% ethanol, this study has demonstrated that 70% ethanolic extract of Manilkara Zapota (L.) P. Royen Fruit Peel (MZFP) has the highest in vitro free radical scavenging potential as compared to extracts of ot...
Bulletin of the National Research Centre
Background A perusal of the literature suggested that Manilkara zapota (L.) P. Royen stem bark (M... more Background A perusal of the literature suggested that Manilkara zapota (L.) P. Royen stem bark (MZSB) is enriched with several bioactive phytoconstituents but had not been yet screened for its in vitro and in vivo antidiabetic potentials. Thus, the present study aimed to investigate the effects of 70% ethanolic extract of Manilkara zapota (L) P. Royen stem bark (EMZSB) in DPPH- and H2O2-scavenging assay, in vitro α-glucosidase inhibition assay, ameliorating diabetes and its complications in alloxan-induced diabetes in Wistar rats. Results With a maximum extractive yield of 9.16% w/w, EMZSB has shown the presence of various phytochemicals like flavonoids, phenolic compounds, tannins, anthraquinone glycosides, steroids, terpenoids, and alkaloids. EMZSB has elucidated a considerable in vitro free radical scavenging potential by DPPH and H2O2 assays when compared with absolute ethanolic extract of Manilkara zapota (L) P. Royen stem bark (AEMZSB), while ascorbic acid was taken as the sta...
Indian Journal of Pharmaceutical Sciences, 2020
Karale et al.: Antiobesity potential of bitter melon Momordica charantia L. grows in many tropica... more Karale et al.: Antiobesity potential of bitter melon Momordica charantia L. grows in many tropical and subtropical regions, the fruits of which are gradually becoming popular for treating diabetes and associated diseases. Momordica charantia L. appears to be an inimitable species that synthesizes a diverse range of chemical constituents in the fruits, leaves, stem and roots. Over 248 compounds belonging to the lipids, phenolics and terpenoids classes have been reported in various studies. The cucurbitane types of triterpenes exist in various parts of this plant as aglycones as well as glycosylated forms. Momordica charantia L. has been comprehensively studied worldwide for therapeutic properties to treat a number of diseases like diabetes, dyslipidaemia, obesity and certain cancers. The bitter melon seems to exert lipid lowering and antiobesity effects via several mechanisms like PPARs, LXRs, SREBPs, and Sirts-mediated fat metabolism in various tissues, prevent adipocyte hypertrophy and visceral fat accumulation. This article presents an extensive literature review on the vast potential of bitter melon as antiobesity agent with supporting data on complex phytochemistry.
Journal of Diabetes & Metabolic Disorders, 2022
This study aims to evaluate the effects of Manilkara zapota (L) P. Royen fruit peel extract (EMZF... more This study aims to evaluate the effects of Manilkara zapota (L) P. Royen fruit peel extract (EMZFP) and its fractions in ameliorating diabetes and its complications in alloxan and STZ-NA induced diabetes in Wistar rats. Antidiabetic effects of EMZFP were assessed in alloxan (150 mg kg-1) induced diabetes in differently grouped rats (n=6). Diabetic rats were treated with EMZFP 150, 300, and 600 mg kg-1 while, glimepiride (0.09 mg kg-1) was used as a reference standard. Treated animals were assessed for various biological parameters i.e. blood glucose, serum lipids, nephroprotective markers, cardiovascular risk indices, liver glycogen, neuropathy, body weight, and histopathology of kidneys. However, for evaluating antidiabetic effects of fractions (chloroform, acetone, ethyl acetate, and remaining ethanol fraction) of EMZFP, diabetes was induced by streptozotocin (60 mg kg-1)–nicotinamide (120 mg kg-1/ml) in differently grouped male rats (n=6). Diabetic rats were treated with EMZFP fractions 200 mg kg-1 however; glibenclamide (10 mg kg-1) was a reference standard and evaluated for blood glucose, serum lipids, cardiovascular risk indices, and diabetic neuropathy. EMZFP 300 and 600 mg kg-1/day demonstrated significant antihyperglycemic effects with augmentation in glycogen content, perfection in serum lipid profile, cardiovascular risk indices, body weight enhancement, nephroprotective effects, beneficial in peripheral neuropathy, and histopathological evidence of reversal of glomerulosclerosis. EMZFP-Et and EMZFP-EA fractions depicted a significant improvement in blood glucose, serum lipid profile, cardiovascular risk indices, and peripheral neuropathy. EMZFP and its Et and EA fractions ameliorated diabetes and its complications by improving glycemic control and associated biochemical alteration. • Manilkara Zapota (L.) P. Royen fruit peel 70% ethanolic extract exert antidiabetic effects • EMZFP significantly ameliorated diabetic biochemical parameters and its complications. • EMZFP-Et and EMZFP-EA fractions exert potential antihyperglycemic, hypolipidemic effects and significantly improved cardiovascular risk indices, and peripheral neuropathy. • Studied MZFP can be used as promising natural herbal source of antidiabetic principles.
Future Journal of Pharmaceutical Sciences, 2021
Background Luffa cylindrica (L.) is a commonly used vegetable in different parts of Asia. Its fru... more Background Luffa cylindrica (L.) is a commonly used vegetable in different parts of Asia. Its fruits are generally used as a vegetable, but pharmacological activities of the leaves were unrevealed. The study evaluated the antihyperlipidemic activity and in vitro antioxidant potential of methanolic extract of Luffa cylindrica (L.) leaves (MELCL). The antihyperlipidemic potential was investigated in Triton X-100-induced hyperlipidemic rats. Animals were pre-treated with Triton X-100 (400 mg/kg). The Triton X-100-treated animals were then treated with MELCL at the doses of 100 and 200 mg/kg using 5% CMC, as a vehicle, per oral (p.o) for 7 days. Antioxidant activity was studied by examining the DPPH and hydrogen peroxide radical scavenging potential of the extract. Results The plasma sample of rats was analyzed, and it was found that MELCL shows significant (p
International Journal of Advance Research, Ideas and Innovations in Technology, 2018
Worldwide cancer is the leading cause of death; leukocytes within tumors and at the sites of chro... more Worldwide cancer is the leading cause of death; leukocytes within tumors and at the sites of chronic inflammation provided the first indication of a possible link between inflammation and cancer. Inflammation plays a crucial role at different stages of tumor growth via. transcription factors and inflammatory mediators such as TNF, IL’s, chemokines COX-2, STAT3and NF-κB. Nuclear factor-kappa B (NF-κB) has been one of the most extensively investigated transcription factors for its role in cancers. The NF-κB signaling pathways are vital in the initiation and progression of cancer which can act as a node of pharmacological interference in the management of tumor. However, NF-κB is an essential player in the immune response against various cancer developments; hence inhibition of NF-κB seems to be always important in the treatment of various malignancies. The application of an NF-κB inhibitor may prove useful in anticancer therapy by converting anti-apoptosis effect of NF-κB into apoptot...
A novel series of N-(substituted pyridine-2-yl)-N-(quinoline-2-yl) malonamide derivatives (AK1-AK... more A novel series of N-(substituted pyridine-2-yl)-N-(quinoline-2-yl) malonamide derivatives (AK1-AK24) has been rationally designed, synthesized and biologically screened for in vitro anti HIV activity by using reverse transcriptase assay kit (Roche). Out of the synthesized compounds, compound AK1, AK2 and AK3 show potent reverse transcriptase (RT) inhibitor activity and compounds AK4 to AK9, AK11, AK12, AK13 and AK14 show RT inhibitory activity comparable with standard rilpivirine. In docking studies, those compounds show higher G-Score which indicates higher percentage of inhibition of reverse transcriptase during in vitro screening. In silico pharmacokinetic studies imply that synthesized derivatives have no CYP450 inhibition, no BBB penetration and good oral absorption. Virtual toxicity studies performed by using Toxtree-v 2.6.6 in various computational animal models show high LD50 values and the compounds are found to be non-carcinogenic.
Polymer-drug conjugates have demonstrated several advantages over the corresponding parent drugs,... more Polymer-drug conjugates have demonstrated several advantages over the corresponding parent drugs, including fewer side effects, enhanced therapeutic efficacy, ease of drug administration, and improved patient compliance. Polymer-drug conjugates are nano-sized hybrid constructs that covalently combine a bioactive agent with a polymer to ensure not only its efficient delivery to the required intracellular compartment but also its availability within a specific period of time. Polymer-drug conjugates such as HMPA Copolymer-Doxorubicin (PK1), HMPA Copolymer-Doxorubicin-Galactosamine (PK2), HMPA CopolymerCamptothecin, HMPA Copolymer-Platinate (AP5346), PEG-Camptothecin (Pegamotecan) and PEG-SN38 (EZN2208) have main role in treatment of a wide variety of human pathologies, from diabetes, heart failure, and brain stroke. Future generation of polymer-drug conjugates will have to meet a number of challenges, including the development of novel polymers with modulated rates of degradation, ver...
A novel series of substituted 2-Amino-4,6-diarylpyr imidines (DAPY’s)as Non-nucleoside reverse tr... more A novel series of substituted 2-Amino-4,6-diarylpyr imidines (DAPY’s)as Non-nucleoside reverse transcri ptase inhibitors (NNRTIs) were designed, synthesized and evaluated for in vitro reverse transcriptase (RT) i nhibition activity. Out of the reported compounds, 4a 4i, 4j and 4n showed potent anti-HIV activity as compared to stan dard rilpivirine. The other compounds displayed moderate activity against HIV-1. Binding affinities of the d signed NCEs were studied on reverse transcriptase enzyme using docking studies and showed possible horseshoe confo rmati n as required for the DAPY category of RT inhibitors. A correlation was found between the anti-HIV activity and the electrostatic energy interaction with Lys 101 resid ue.
Uploads
Papers by Shashikant Dhawale