Browsing by Author "Shukla, Paritosh"

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Chemically cross-linked polysaccharides for biomedical applications
(Elsiever, 2020) Shukla, Paritosh
The significance of polysaccharides as the building blocks in the domain of biology and pharmacy has been tremendously increasing. This can be owed to their outstanding attributes such as biodegradability, chemical modification, homogeneity, compatibility with the biological system, low cost, and toxicity. The chemical modification of these biopolymers is promoted by functional moieties on the polysaccharide chains. Nevertheless, their aqueous instability and a lack of required mechanical strength are considered as the major obstacles for the medical applications involving these biopolymers. As a result, the derivatization of the polysaccharides is under investigation for the enhancement of their mechanical properties, which is also important from the formulation point of view. This has led to the use of the cross-linking technique as a stabilization process for designing cross-linked polysaccharides for biomedical applications. Different types of physical, enzymatic, and chemical methods are accessible for establishing the cross-linkages between the polysaccharide chains. An extensive range of methods such as cross-linking with aldehydes, the addition and condensation reactions, free-radical polymerization, and high-energy radiations mediated cross-linking are presented for achieving chemical cross-linking. Hence, these methods are employed for the formation of chemically cross-linked polysaccharides for biomedical usage, including the production of biofilms, polysaccharide-based hydrogels, cross-linked polysaccharide sponges, and regular/ultrafine fibers. In this chapter, different types of cross-linking techniques, along with the significance of chemical cross-linking techniques with relevant biomedical applications have been discussed in detail.
ChemInform Abstract: Novel Grinding Synthesis of Pyranopyrazole Analogues and Their Evaluation as Antimicrobial Agents.
(Wiley, 2016) Jha, Prabhat N.; Shukla, Paritosh
Compounds are prepared and screened for their antibacterial and antifungal activities
Cobalt-Catalyzed Reductive Coupling of Saturated Alkyl Halides with Activated Alkenes Paritosh Shukla, Yun-Chu Hsu and Chien-Hong Cheng
(OCP, 2006) Shukla, Paritosh
An efficient cobalt-catalyzed reductive coupling reaction of alkyl halides with alkenes bearing electron-withdrawing groups in the presence of water and zinc powder in acetonitrile gave the corresponding Michael-type addition products in high yields. The mechanism is discussed.
Current pharmacophore based approaches for the development of new anti-Alzheimer’s agents
(Elsevier, 2024-11) Shukla, Paritosh
Amyloid beta peptide (Aβ) and hyperphosphorylated neuronal tau proteins accumulate in neurofibrillary tangles in Alzheimer’s disease (AD), a chronic neurodegenerative illness. Chronic inflammation in the brain, which promotes disease progression, is another feature of the Alzheimer’s disease pathogenesis. Approximately 60–70 % of dementia cases are caused by AD. The development of effective therapies for the treatment of AD is urgently needed given the severity of the condition and its rapidly rising prevalence. Cholinesterase inhibitors, beta-amyloid (A-beta), tau inhibitors, and many other medications are currently used as preventive medicine for AD. These medications can temporarily suppress dementia symptoms but cannot halt or reverse the disease’s progression. Many international pharmaceutical companies have tried numerous times to develop an amyloid clearing medication based on the amyloid hypothesis, but without success. Therefore, the amyloid theory may not be entirely plausible. This review mainly covers the recent and important reported pharmacophores as the starting point to discuss already known targets like tau, butyrylcholinesterase, amyloid beta, and acetylcholinesterase and covers the literature between years 2019–2024.
Cyclization of Oxa-Bicyclic Alkenes with β-Iodo-(Z)-propenoates and o-Iodobenzoate Catalyzed by Nickel Complexes: A Simple Efficient Route to Annulated Coumarins
(ACS, 2003) Shukla, Paritosh
In the presence of Ni(dppe)Br2 and Zn powder in acetonitrile at 80 °C, oxa-bicyclic olefins undergo cyclization with o-iodobenzoate and with β-iodo-(Z)-propenoates to give the benzocoumarin derivatives in moderate to good yields. This methodology offers a simple efficient way for the synthesis of structurally complicate coumarins in one pot.
Development of a low cost potato gel system for nitrate removal from water
(RJCE, 2016-09) Shukla, Paritosh; Gupta, Rajiv; Singhal, Anupam
This paper proposes to utilize the commonly available natural resource in form of tuber i.e. potato to treat the water for nitrate. The gel derived from potato (Solanum tuberosum) is employed for the removal of contaminant present in the water. The chosen system has shown overall 92 % reduction in nitrate concentration. Batch study was carried out to optimize the parameters (time of reaction, adsorbent weight and adsorbate concentration) followed by 144 h run of column to determine capability of adsorbent with artificial samples. Our studies showed that the batch study followed the Langmuir isotherm more closely than the Freundlich isotherm. Column data fit the Thomas model and kinetic constant is determined using Thomas equation. The maximum sorption capacity determined for adsorbent is 0.2484 mg/g. FTIR analysis of adsorbent (potato gel) at two different conditions shows changes in transmittance indicating the presence of active sites in adsorbent responsible for nitrate reduction.
Developments and challenges in biodiesel production from microalgae: A review
(2015-07-14) Shukla, Paritosh; Mehrotra, Sandhya Amol; Mehrotra, Rajesh
The imminent depletion of fossil fuels and the surging global demand for renewable energy have led to the search for nonconventional energy sources. After a few decades of trial and error, the world is now testing the sources of the third generation of fossil fuels, which contain for most parts microalgae. With more than 80% oil content, being adaptable in growth parameters and highly versatile, microalgae are highly promising sources of biofuels in the present time. The present article makes a sweeping attempt to highlight the various methods employed for cultivation of microalgae, techniques to harvest and extract biomass from huge algal cultures, as well as their downstream production and processing procedures. The advantages, limitations, and challenges faced by each of them have been described to some extent. Major concerns pertaining to biofuels are supposed to be their environmental sustainability and economic viability along with their cost effectiveness. This would require a great deal of empirical data on existing systems and a great deal of optimization to generate a more robust one. We have concluded our article with a SWOT analysis of using algae for biodiesel production in a tabulated form.
Diazapentacene Derivatives as Thin-Film Transistor Materials: Morphology Control in Realizing High-Field-Effect Mobility
(ACS, 2009) Shukla, Paritosh
5,7,12,14-Tetrachloro-6,13-diaza-6,13-dihydropentacene (TCDAHP) and 5,7,12,14-tetrachloro-6,13-diazapentacene (TCDAP) were synthesized and assessed as the active channel materials for thin-film transistor applications. Analyses of the crystal structures of these molecules revealed that both exhibited slipped π−π stacking of the long and fused aromatic moiety. Although the packing features of the two compounds are basically identical, their highest occupied molecular orbitals, which are relevant to hole transport, are very different. Better mobility was predicted for TCDAHP over TCDAP based on the dimeric structure in the X-ray coordinates. The morphologies of thin films of TCDAHP and TCDAP prepared by thermal evaporation depend critically on the substrate on which the molecules were deposited: from the amorphous state on a SiO2/Si surface to the crystalline state on a pentacene buffer layer surface. The performance of thin-film transistors prepared on various substrate surfaces was studied. While no field-effect mobility was observed for these films deposited on SiO2/Si, a high mobility of 1.4 cm2/(V s) for the TCDAHP film was achieved when deposited on a pentacene buffer layer prepared on a rubbed monolayer of n-nonyltrichlorosilane on a SiO2/Si surface. A similar device prepared from TCDAP gave a mobility of 0.13 cm2/(V s).
Facile β-Alkyl and β-Hydride Elimination in the Nickel-Catalyzed Annulation of o-Iodophenyl Ketones and Aldehydes with Bicyclic Alkenes
(ACS, 2006-05-26) Shukla, Paritosh
o-Iodoaryl aldehydes react with bicyclic alkenes in the presence of NiBr2(dppe) and Zn powder in acetonitrile at 80 °C undergoing annulation to give polycyclic ketone derivatives. Surprisingly, o-iodoaryl alkyl ketones also react with bicyclic alkenes to form polycyclic ketones with structures the same as those from the corresponding o-iodoaryl aldehydes.
Fast Microwave Assisted Synthesis of Pyranopyrazole Derivatives as New Anticancer Agents
(Bentham Science, 2016) Chowdhury, Rajdeep; Shukla, Paritosh
A series of compounds having the pyranopyrazole pharmacophore were synthesised by the traditional method and then by an unreported rapid four-component microwave assisted method. The microwave strategy required substantially shorter reaction times as compared to the traditional method. The prepared molecules were tested in-vitro for their cytotoxic activity against the Hep3B cancer cell lines. The activity results were subsequently rationalized for a quick structure-activity relationship leading to the conclusion that the presence of certain heteroatom substituents at a 3-position of the pharmacophore may be crucial for anticancer potency.
Food additives from an organic chemistry perspective
(MoJ, 2017-08-04) Shukla, Paritosh
Food additives are an essential part of the contemporary food system, providing definite advantages in terms of people’s way of life. Food additives have been used, investigated, regulated, and controlled all through history. Although many reports, books, monographs, articles, etc. are available on this topic, but only a few of them focus on catering primarily to an organic chemistry audience who has little or no prior exposure to systematic food additive chemistry. This report gives a brief historical and regulatory background followed by an overview of different types of food additives along with their properties and structures. The paper is roughly subdivided into the following categories: (a) introduction to food additives, (b) their brief historical background, (c) short introduction to the numbering and the approval process for additives, (d) a discussion of the categories of food additives from an organic chemists’ perspective which forms the main bulk of the paper including, for example, categories such as acids, acidity regulators, antifoaming and anticaking agents, emulsifiers, flavors, etc., (e) comparison of organic vs synthetic foods and food safety issues, and (f) conclusion and future prospects.
Functionalized pyranopyrazole molecules as corrosion inhibitors for mild copper metal in HCl solution: synthesis, theoretical studies, and physical investigations
(IOP, 2018-02-07) Shukla, Paritosh; Manohar, Prashant Uday; Pande, Surojit; Dalvi, Anshuman
Five substituted pyranopyrazole (PPZ) derivatives were chemically synthesized by conventional and microwave assisted synthesis (MWA) methodology. Their differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) analyses, and the corrosion inhibitor properties on mild copper metal in 1 M HCl solution were investigated by SEM (Scanning Electron Microscopy), EDS (Energy Dispersive Spectroscopy), and XRD (x-ray Diffraction) all of which showed good anti-corrosion behavior. Further, mechanical property investigations were also performed by measuring the tensile strength of the PPZ-adsorbed Cu-strips. Finally, the inhibition action was evaluated by quantum chemical parameters. All the experimental results pointed that the molecules acted as excellent anti-corrosion surface active agents for copper metal.
Green Synthesis, in-vitro Antimicrobial Evaluation, Docking, and SAR Studies of Potent Quinoline-4-Carboxylic Acids
(Bentham Science, 2019) Jha, Prabhat N.; Murugesan, Sankaranarayanan; Shukla, Paritosh
The paper describes the synthesis of quinoline-4-carboxylic acid derivatives employing completely green methods such as the use of water as solvent and of microwave irradiation for heating. The prepared molecules were examined for bactericidal and antifungal behavior and two of the tested compounds showed reasonably good antimicrobial activity. The biological activity results were further corroborated by fluorescence microscopy and by evaluating their time-dependent bactericidal behavior. Two of the most potent compounds were then subjected to docking against DNA gyrase protein (PDB ID: 2XCT) showing possible interactions responsible for the potency of these compounds. Also, an SAR analysis was proposed based on the results obtained
Nickel-catalyzed reductive Heck type coupling of saturated alkyl halides with acrylates and oxabenzonorbornadiene
(Elsiever, 2015-04-15) Shukla, Paritosh
The Heck reaction is a well-established transition-metal catalyzed reaction for coupling alkenes with sp2 alkyl halides to give novel unsaturated compounds. Herein we report an analogous Heck-inspired, simple efficient coupling of sp3 alkyl halides with electron-withdrawing alkenes to form reductive coupling products where saturated esters are obtained. A range of acrylates were coupled with sp3 alkyl halides in the presence of Ni(PPh3)2Cl2 catalyst, Zn metal powder, CH3CN solvent, and water, at 80 °C to form the reductive Heck type saturated ester products in good yields. This strategy was further extended to couple oxabenzonorbornadiene with the alkyl halides resulting in ring opening to give rise to bicyclic alcohol products. The mechanism for both the reactions appears to be the usual oxidative-addition driven alkene insertion reaction where the water appears to act as the protonating agent.
Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies
(Thieme, 2019) Shukla, Paritosh; Chowdhury, Rajdeep
Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental finding
Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies
(Bentham Science, 2019) Chowdhury, Rajdeep; Shukla, Paritosh; Sharma, Ashok
Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.
De novo Design and in-silico Studies of Coumarin Derivatives as Inhibitors of Cyclin Dependent Kinase-2
(JPC, 2017-10-31) Shukla, Paritosh; Murugesan, Sankaranarayanan
In the present study, around sixty-two novel coumarin derivatives were designed as CDK-2 inhibitors based on essential pharmacophoric requirements. All the designed compounds were subjected to docking study using AutoDock 4.2 against CDK-2 protein (PDB ID: 1HCK). Molinspiration and Osiris property explorer were used to predict Lipinski’s rule of five and toxicity profile. The Structure Activity Relationship study revealed that, the substitution at R1 and R4 of coumarin nucleus enhances the binding energy and inhibitory constant values from nanomolar to picomolar range. Among the designed analogues, compound 15, 28, 43 and 59 showed significant binding energy and inhibitory constant values as compared to the standard drug Olomoucine and Deschloroflavopiridol. Most of the designed analogues showed similar binding mode and orientation inside the active site of the protein as that of the standard drug, which strongly indicates that the designed molecules may emerge as potent inhibitors of CDK-2. Next, molecular dynamics study of the significantly active molecule 15 was studied for 10 ns, in order to determine the stability of the coumarin molecules inside the binding cavity of the protein. In-silico investigations suggest that the de novo designed coumarin derivatives were potentially in-silico bioactive and need to be synthesized and tested further.
Quinoline Glycoconjugates as Potentially Anticancer and Anti-Inflammatory Agents: An Investigation Involving Synthesis, Biological Screening, and Dockin
(ECSP, 2020-08-20) Dubey, Uma S.; Sah, Ajay Kumar; Shukla, Paritosh
The present work is a preliminary report of synthesis of a series of targeted 4,6-O-ethylidene-β-D-glucopyranosylamine glycoconjugate quinoline 4-carboxylic acid derivatives followed by a quick evaluation of their anti-inflammatory and anticancer activities. Compounds C5 and C8 exhibited highest anti-inflammatory activity against human COX-2 enzyme. Anticancer studies were also performed in vitro which revealed C8 as a promising candidate against HeLa, human cervical cancer cell lines. The anti-inflammatory and anticancer activity was further confirmed by molecular docking studies for all the synthesized molecules. That all the compounds showed potency, seems to validate our initial hypothesis concerning a positive correlation between anticancer and anti-inflammatory activity for the designed quinoline glycoconjugates.
Scaffold-Hopping Strategy: Synthesis and Biological Evaluation of 5,6-Fused Bicyclic Heteroaromatics To Identify Orally Bioavailable Anticancer Agents
(ACS, 2011-03-24) Shukla, Paritosh
Utilizing a scaffold-hopping drug-design strategy, we sought to identify a backup drug candidate for BPR0L075 (1), an indole-based anticancer agent. For this purpose, 5,6-fused bicyclic heteroaromatic scaffolds were designed and synthesized through shuffling of the nitrogen from the N-1 position or by insertion of one or two nitrogen atoms into the indole core of 1. Among these, 7-azaindole core 12 showed potent in vitro anticancer activity and improved oral bioavailability (F = 35%) compared with 1 (F < 10%).
Sensing of contaminants in potable water using TiO2 functional film
(AIP, 2016) Shukla, Paritosh; Manjuladevi, V.; Gupta, Raj Kumar
The piezoelectric based quartz crystal microbalance is employed for sensing contaminants in potable water. A spin coated thin layer of TiO2 nanoparticles was formed at the sensing area of a 5 MHz AT-cut quartz wafer. The thin film of TiO2 nanoparticles forms a mesoporous functional layer for the trapping of water borne contaminants. The morphology of the thin film of TiO2 nanoparticles was studied using field emission scanning electron microscope (FESEM). The surface morphology of the TiO2 nanoparticles reveals the mesoporous structures indicating large number of defects and porous sites. Such film was employed for the detection of water borne contaminants by detecting the piezoelectric response from a quartz crystal microbalance. We found the film to be very sensitive to the contaminants. The minimum detection limit was found to be 330 ppb. The effect of surface recharging was also studied by altering the physical conditions so that the film can be used for repetitive usage.