Adarsh sahu | Dr. Hari Singh Gour University, Sagar (A Central University) (original) (raw)

Papers by Adarsh sahu

Current Organic Chemistry

: The utility of quinazoline scaffolds as intermediates in new medicinal drug development and dis... more : The utility of quinazoline scaffolds as intermediates in new medicinal drug development and discovery has grown in recent decades. The quinazoline framework is a valuable pharmacophore, intermediate, and interesting building block with a wide range of pharmacological activities that has piqued the interest of researchers in developing novel synthetic strategies in medicinal chemistry. In contrast to time-, solvent-, and energy-consuming separation approaches, magnetic separation is an effective method for the quick separation of catalysts from reaction media. Nowadays, magnetically separable nanoparticles have recently gained much interest from chemist in recent research due to their remarkable catalytic activity in various chemical transformations. Many research articles have been published for the synthesis of quinazoline derivatives based on utilizing nanoparticles as a catalyst because of the significant role that biological quinazoline plays in medicinal chemistry. In the present review study, we summarize the surface functionalization of mesoporous silica, metal organocatalysts, ionic liquids, and polymer-supported magnetic nanoparticles and their applications as magnetically recoverable nanocatalysts in the efficient synthetic methods of biologically active quinazoline and its derivatives.

Letters in Drug Design & Discovery

: In the past two decades, targeted cancer therapy has emerged as a novel class of anticancer the... more : In the past two decades, targeted cancer therapy has emerged as a novel class of anticancer therapeutics besides traditional chemotherapy, surgery, and radiotherapy. There is an extensive variety of anticancer drugs in the market, and several compounds are in various stages of clinical trials. Many studies indicate that these cytotoxic molecules are also associated with various types of toxicity and contrary side effects; thus, researchers all over the world are working to develop more effective and safer anticancer drugs. 1,3-thiazole derivatives have recently been identified as a novel class of cancer chemotherapeutic agents with promising activity against various tumors. In this review, we have systematically summarized and highlighted the latest developments in 1,3-thiazole derivative for anticancer activity.

Combinatorial Chemistry & High Throughput Screening

: The advancement of computing and technology has invaded all the dimensions of science. Artifici... more : The advancement of computing and technology has invaded all the dimensions of science. Artificial intelligence (AI) is one core branch of Computer Science, which has percolated to all the arenas of science and technology, from core engineering to medicines. Thus, AI has found its way for application in the field of medicinal chemistry and heath care. The conventional methods of drug design have been replaced by computer-aided designs of drugs in recent times. AI is being used extensively to improve the design techniques and required time of the drugs. Additionally, the target proteins can be conveniently identified using AI, which enhances the success rate of the designed drug. The AI technology is used in each step of the drug designing procedure, which decreases the health hazards related to preclinical trials and also reduces the cost substantially. The AI is an effective tool for data mining based on the huge pharmacological data and machine learning process. Hence, AI has been used in de novo drug design, activity scoring, virtual screening and in silico evaluation in the properties (absorption, distribution, metabolism, excretion and toxicity) of a drug molecule. Various pharmaceutical companies have teamed up with AI companies for faster progress in the field of drug development, along with the healthcare system. The review covers various aspects of AI (Machine learning, Deep learning, Artificial neural networks) in drug design. It also provides a brief overview of the recent progress by the pharmaceutical companies in drug discovery by associating with different AI companies.

Anti-Cancer Agents in Medicinal Chemistry

: Presently, several protein kinases have been discovered with the aim to treat various cancers. ... more : Presently, several protein kinases have been discovered with the aim to treat various cancers. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that plays a role in the pathogenesis of a wide variety of human cancers known as ALCLs, NSCLC, ovarian cancer, breast cancer, colorectal cancer, neuroblastoma, etc. The fulllength ALK receptor is a classical receptor tyrosine kinase composed of an amino-terminal extracellular domain and an intracellular tyrosine kinase domain. Crizotinib is a strong oral small-molecule first tyrosine kinase inhibitor of ALK to be used in the treatment of ALK-dependent NSCLC. Due to the drug resistance of first generation ALK inhibitors, researchers are trying to design and synthesize novel ALK inhibitors with various heterocyclic rings in which 2,4- diarylaminopyrimidine derivatives with a specific N-(3-pyridinylmethyl)urea moiety, 2-amino-4-(1-piperidine) pyridine derivatives, 7-azaindole and carboxamide derivatives and some others produced potential compounds. To overcome drug resistance, to get better affinity and to reduce drug toxicity, there is an urgent need for novel ALK inhibitors. The present review describes the ALK signaling, their inhibitors and related structure activity relationships for the development of potential ALK inhibitors.

International Journal of Quantitative Structure-Property Relationships, 2021

Myeloid cell leukemia (Mcl-1) protein, belonging to a large BCL2 family of proteins, is a signifi... more Myeloid cell leukemia (Mcl-1) protein, belonging to a large BCL2 family of proteins, is a significant target towards cancer chemotherapy. The over-expression of this protein is also responsible for the development and progression of severe multi-drug resistance in cancer patients. This present study has focused the attention towards unmasking of important structural fingerprints for promoting or hindering Mcl-1 inhibitory activity of some indole-based derivatives by using Monte Carlo optimization-based QSAR approach. Twenty-one robust classification models were generated. The best model (by using SMILES and HSG-based descriptors) was selected, and several important good and bad structural fingerprints for Mcl-1 inhibition were identified. Some of the fingerprints were matching with the earlier study (New J. Chem., 2020, 44, 17494-17506) and some new fingerprints were also generated. The modelling study will help the researchers in the lead optimization of some indole-based Mcl-1 inh...

International Journal of Pharmaceutical Chemistry, 2015

An isocratic, precise and accurate reversed-phase liquid chromatographic method was developed for... more An isocratic, precise and accurate reversed-phase liquid chromatographic method was developed for the quantitative determination of Azithromycin in tablet dosage form. The separation was carried out using a mobile phase consisting of buffer Potassium dihydrogen Phosphate: Acetonitrile (HPLC grade) (pH 7.5 adjusted with ortho phosphoric acid). The column used was Hypersil- keystone C18 (250 X 4.60 mm), 5?m column with flow rate of 1.2 ml/min using U.V. Visible detector. The detection was monitored at 215nm and the run time was 25min. The volume of injection loop was 10?l prior to injection of the drug solution the column was equilibrated for at least 15 min. The retention times of Azithromycin were found to be 9.761. Results of analysis were validated statistically and by recovery studies. Forced degradation method is used for detection of degraded impurities in body fluids shows better results than reported. The results of the study conclude that the proposed RP-HPLC method is a sim...

Anti-Infective Agents, 2021

: The colchicine binding site in microtubules is the most flourishing target for anti-cancer trea... more : The colchicine binding site in microtubules is the most flourishing target for anti-cancer treatment. Microtubule inhibitor drugs, including paclitaxel and vinca alkaloids, have been considered to exert their activity primarily by increasing or decreasing the cellular micro-tubule mass. This review describes the microtubular assembly along with the combretastatin de-rivatives as microtubules inhibitors, the structures of compounds known to interact with colchi-cines binding sites, and their possible mechanism of action. Additionally, the utility of other heterocyclic rings and their combretastatin derivatives in treating cancer is also discussed. Col-chicines binding site represents a stimulating new molecular target in the design of com-bretastatin drugs.

Current Organocatalysis, 2021

Background: 1,2,3-triazole is considered a widely explored scaffold by medicinal chemists because... more Background: 1,2,3-triazole is considered a widely explored scaffold by medicinal chemists because of its therapeutic importance. The structural characteristics of 1,2,3-triazoles allow it to mimic certain functional groups demonstrating its utility to prepare new medicinal compounds using the concept of bioisosterism and molecular hybridization. Centered on Huisgens cycloaddition reaction, over the past decade and a half, developed click chemistry approaches to furnish triazole derivatives with various applications ranging from drugs to bioconjugation linkers. Objective: In the present review, we aim to highlight the different approaches developed for the synthesis of 1,2,3-triazole derivatives and in particular, advances in synthetic methods for the last 16 years. This review is also intended to help researchers for finding potential future directions and scope in the development of synthetic strategies. Conclucion: As summarized through the compilation of recent advances for 1,2,3...

Current Nanotoxicity and Prevention, 2021

Nanotoxicity has become the topic of great concern in nanoscience and nanotechnology because of t... more Nanotoxicity has become the topic of great concern in nanoscience and nanotechnology because of the increasing toxic effects of nanomaterials on living organisms. The toxic patterns of chemotherapeutic drugs, nanomedicines, and nanocarrier are closely associated. Long term exposure of nanocarrier composed of several bioactive (protein and peptide drugs) and chemotherapeutic drugs (anticancerous agents) leads to toxicity, selective induction of cytotoxicity in normal cells and organ. Important factors that contribute directly and significantly to the toxicity of nanoparticles (NPs) constitute particle size, shape and surface area. Apart from size and shape, the structure of the NPs also contributes to nanotoxicity. The review focuses on the basic perceptions and mechanisms of nanomaterial-based drug delivery and nanotoxicity is introduced along with a detailed classification of drug delivery approaches i.e., carbon nanotubes, Quantum dots, fullerenes and NPs and nanotoxicity models, ...

Current Chemical Biology

Background: Leishmaniasis is a multifaceted disease that is prevalent worldwide. It is an epidemi... more Background: Leishmaniasis is a multifaceted disease that is prevalent worldwide. It is an epidemic, tropical/subtropical disease caused by macrophage infection by compulsive leishmania genus intracellular parasites affecting millions of people across the globe. Methods: The demand for effective and safe molecules in the field of leishmaniasis is still an active research area. The lack of widely effective anti-leishmanial drugs, therefore, means a critical need for the production of modern, effective, affordable, and safe drugs for leishmaniasis care. In the recent past, many new pharmacophores have been synthesized and evaluated for their antileishmanial activity. Conclusion: Many important heterocycles have proved to be effective against various leishmanial strains in terms of both safety and efficacy. In this article, we have attempted to review the different pharmacophores discovered in the past few years with the potential anti-leishmanial property.

Anti-Infective Agents

Background: Reduced efficacy of the available antifungal drugs is the major public health concern... more Background: Reduced efficacy of the available antifungal drugs is the major public health concern of the population all over the world. Despite significant advances in the treatment of these life-threatening infections, severe toxicity and increasing median effective dose have lim-ited the efficacy of frontline therapy applicable against them. Objective: The quintessential occurrence of systemic toxicity handicaps the clinical utility of cur-rently available antifungal drugs. 1,2,3-Triazoles in the same context are relatively less toxic. Con-sequently, conjugation of quinine with the triazole moiety for enhanced efficacy and reduced tox-icity have been excessively envisaged and reported in the context of a range of activities ranging from inflammation to cancer, however lack of toxicity profile sabotages the translation of the la-boratory prototype into successful clinical practice. Method: We herein report the synthesis and characterization of a series of quinine triazole hybrids v...

Current Organic Synthesis, 2018

Aim and Objective: Phosphonate possesses a broad range of applications ranging from agrochemistry... more Aim and Objective: Phosphonate possesses a broad range of applications ranging from agrochemistry to medicines. Because of the synthetic and biological importance of phosphonate, their chemistry has stimulated an increasing interest. Hence we developed an efficient and eco-friendly Mg(ClO4)2 catalyzed one pot, solvent free synthesis of phosphonate derivatives of chalcones. Materials and Methods: Magnesium perchlorate phosphonate derivatives of chalcones were synthesized. The reactions were executed at room temperature in the presence of Anhydrous Magnesium perchlorate Anhy. Mg(ClO4)2 under solvent free condition, affording high yield of the product. The cardinal significance of the method lies in its uncomplicated and eco- friendly experimental conditions. Results: The PMA method for P-C bond formation, using dialkyl phosphite with chalcone, was performed in the presence of Anhydrous Magnesium perchlorate under solvent free condition. Despite the solvent free condition, the methodol...

Current Chemical Biology, 2020

Motivated by evidence garnered from literature probing the use of triazoles in drug discovery and... more Motivated by evidence garnered from literature probing the use of triazoles in drug discovery and development, we reported the utilization of bioisosteric replacement and molecular hybridization in this review. Bio-isosteric replacement has played a significant role in modulating rapid and versatile strategy in synthesizing molecules with multifaceted medicinal properties. Molecular hybridization seeks to conjugate two molecular fragments with diverse applications under very mild reaction conditions. In this regard, 1,2,3-triazole is a well-known scaffold with widespread occurrence in medicinal compounds. It is characterized to have several bioactivities such as anti-microbial, anti-cancer, anti-viral, analgesic, anti- inflammatory effects. Furthermore, the structural features of 1,2,3-triazoles enable it to mimic different functional groups justifying its use as bio-isostere for the synthesis of new molecules of medicinal interest, which we have reported briefly.

Central Nervous System Agents in Medicinal Chemistry, 2019

Objectives: In the current study, the synthesis, characterization, and neuropharmacology of quina... more Objectives: In the current study, the synthesis, characterization, and neuropharmacology of quinazolinone tethered with aromatic (3a-3i) and heteroaromatic substitution (3j, 3k, and 3l) as effective anxiolytic agents are reported. Background: Anxiety and depression are often comorbid with neurological as well as other medical maladies. Clinically known anxiolytics (Benzodiazepines) are accompanied by untoward sedation and other CNS depressive actions. The quinazolinone moiety is a privileged pharmacophore with a wide pharmacological spectrum. Herein, the synthesis, characterization, and neuropharmacological evaluation of some 2-substituted quinazolinone derivatives are reported. Methods: The synthesized compounds were characterized using 1H-NMR and TLC analysis. Behavioral analysis was performed using EPM (Elevated Plus Maze), OFT (Open Field Test), PIST (Pentobarbital Induced Sleep Test), FST (Forced Swim Test) and PCPA (p-chlorophenyl alanine) bioassay. To further justify the ther...

ACS Omega, 2019

A series of hybrid antimicrobial compounds were prepared by carboxylic acid protection of 6-amino... more A series of hybrid antimicrobial compounds were prepared by carboxylic acid protection of 6-aminopenicillanic acid using benzyl alcohol and thionyl chloride succeeded by azide displacement using trifluoromethanesulfonyl azide in dichloromethane. The azide thus formed was reacted with substituted alkynes to furnish benzyl-protected penicillin−triazole conjugates. Benzyl deprotection of the conjugates resulted in furnishing PNTCs under water methanol mixture using Pd/C as a catalyst. The PNTCs (7a−j) formed were screened for in vitro antibacterial potency against pathogenic strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes and antifungal potency against Candida albicans, Aspergillus niger, and Aspergillus clavatus. Further antimicrobial evaluation revealed compounds 7c, 7d, 7e, 7g, and 7i to be the most compounds of the series with minimum inhibitory concentration value for antibacterial in the range 0.5−50 μg/mL and for antifungal in the range 9−300 μg/mL. Toxicological analysis documented for compounds 7c, 7d, 7e, 7g, and 7i revealed compound 7i to be the most promising member of the series with 1000 and 500 mg/kg LD 50 , and no-observed-adverse-effect level to facilitate future clinical studies of the same.

Anti-Infective Agents, 2019

Background: 3,5-Bis(arylidene)-4-piperidinones (BAP) belong to a wide class of cross conjugated d... more Background: 3,5-Bis(arylidene)-4-piperidinones (BAP) belong to a wide class of cross conjugated dienones. The 1,5-diaryl-3-oxo-1,4-pentadienyl fragment of the BAP moiety is responsible for the molecule's anti-tumor, antioxidant, antimicrobial and anti-inflammatory manifestations. In the present study, we present combinations of phosphonate and 3,5-bis(arylidene)-4- piperidone pharmacophores. The anti-inflammatory, anti-oxidant potential, anti-proliferative, cytotoxic potential and antimicrobial of the title compounds were evaluated in in-vitro bioassay paradigms. Methods: A novel class of phosphonate linked 3,5-Bis(aryl methylene)-4-piperidone derivatives were synthesized from simple, versitalie and efficient synthetic methodology. All of the synthesized compounds were screened for their in vitro anti-inflammatory, in vitro anti-oxidant potential, in vitro anti-proliferative, in vitro cytotoxic potential and in vitro antimicrobial activity. Amongst all the synthesized compounds ...

Life Sciences, 2019

, et al., Bio-isosteric replacement of amide group with 1,2,3-triazole in phenacetin improves the... more , et al., Bio-isosteric replacement of amide group with 1,2,3-triazole in phenacetin improves the toxicology and efficacy of phenacetin-triazole conjugates (PhTCs), Life Sciences,

Current Organocatalysis, 2018

Background: Multicomponent reactions (MCRs) are one of the most revolutionary concepts in synthet... more Background: Multicomponent reactions (MCRs) are one of the most revolutionary concepts in synthetic organic chemistry. By definition, an MCR is a convergent chemical process involving three or more reactants to fabricate products which retain all structural and substructural features of the starting materials. The value of MCRs lies in all areas of synthetic chemistry, as they offer shorter reaction time, uncomplicated process protocol and high yield. We here reported a novel, effortless, ecofriendly multi-component one-pot synthesis of potent 2,3-dihydroquinazoline-4(1H)-ones is disclosed. Methods: The method causes condensation of isatoic anhydride, ammonium salts and aromatic aldehydes in ethanol. The reaction further employs metal chloride catalyst and offers significant advantages including the use of green solvent and unsophisticated work-up methodology. Additionally, the method is of value owing to the excellent yield obtained by the reaction. Results: The multicomponent reaction of isatoic anhydride and ammonium chloride with various aldehydes was investigated in presence of ethanol at reflux for 1.5 h. The catalytic MCR of a substituted aldehyde with ammonium chloride and isatoic anhydride generates 10 products with percentage yield ranging from 84-95%. Conclusion: In a nutshell, it can be stated that indium chloride-catalyzed multi-component reaction is a novel and efficient method for the synthesis of 2,3-dihydroquinazoline-4(1H)-ones. Significant advantages of the method include the use of simple and readily available precursors, high yield and easy workup with short reaction times. Better reactivity of ammonium chloride and high catalytic activity of InCl 3 is an added advantage while using ethanol as a green solvent renders the reaction an ecocompatible status.

Bioorganic Chemistry, 2019

A series of hybrid antiprotozoal compounds with quinine-triazolyl scaffold were prepared by coppe... more A series of hybrid antiprotozoal compounds with quinine-triazolyl scaffold were prepared by copper catalyzed Huisgen 1,3-dipolar cycloaddition via O-mesylation with mesyl chloride followed by azide displacement. The synthesized azide derivative was made to react with various aromatic and aliphatic alkynes. The triazolyl-linked quinine scaffolds were synthesized under solvent-free mechanochemical ball milling conditions. Products (6a-s) were screened for in-vitro antimalarial and antileishmanial activity. Screening results indicated that out of the synthesized series of 19 products, compounds 6d, 6h, 6l and 6m showed significant antimalarial (P. falciparum) and antileishmanial activities (L. donavani)

Anti-inflammatory & anti-allergy agents in medicinal chemistry, Jan 2, 2017

Leishmaniasis is a complex devastating disease that is widespread across the globe with 400 milli... more Leishmaniasis is a complex devastating disease that is widespread across the globe with 400 million people in 90 countries at risk of acquiring leishmaniasis. It is caused by intracellular parasites belonging to genus Leishmania. The therapeutic use of commonly available drugs like Pentostam, Glucantime, Amphotericin B, Paramomycin, Miltefosine are declined due to their low efficacy, drug resistance and high toxicity. Therefore, a continuous effort is needed in order to find out less toxic and more successful drugs in future for the handling of leishmaniasis. Interestingly quinazolines derivatives are reported to have promising antileishmanial activities. A number of quinazolines derivatives were synthesized in the past three decades, by means of various synthetic pathways due to their ease of synthesis and favorable physicochemical properties. Thus, this review is focus on various synthetic procedures, chemical characteristics and antileishmanial activities of various quinazoline d...