Dr. Brijesh Rathi
@hansrajcollege.ac.in
Chemistry
Hansraj College, University of Delhi
RESEARCH INTERESTS
Medicinal chemistry and organic chemistry.
Scopus Publications
Scopus Publications
Xiangyi Jiang, Zhen Gao, Prem Prakash Sharma, Sumit Kumar, Brijesh Rathi, Xiangkai Ji, Jiaojiao Dai, Minghui Xie, Guanyu Dong, Shujing Xu,et al.
Wiley
AbstractThe HIV capsid (CA) protein is a promising target for anti‐AIDS treatment due to its critical involvement in viral replication. Herein, we utilized the well‐documented CA inhibitor PF74 as our lead compound and designed a series of low‐molecular‐weight phenylalanine derivatives. Among them, compound 7t exhibited remarkable antiviral activity with a high selection index (EC50 = 0.040 µM, SI = 2815), surpassing that of PF74 (EC50 = 0.50 µM, SI = 258). Furthermore, when evaluated against the HIV‐2 strain, 7t (EC50 = 0.13 µM) demonstrated approximately 14‐fold higher potency than that of PF74 (EC50 = 1.76 µM). Insights obtained from surface plasmon resonance (SPR) revealed that 7t exhibited stronger target affinity to the CA hexamer and monomer in comparison to PF74. The potential interactions between 7t and the HIV‐1 CA were further elucidated using molecular docking and molecular dynamics simulations, providing a plausible explanation for the enhanced target affinity with 7t over PF74. Moreover, the metabolic stability assay demonstrated that 7t (T1/2 = 77.0 min) significantly outperforms PF74 (T1/2 = 0.7 min) in human liver microsome, exhibiting an improvement factor of 110‐fold. In conclusion, 7t emerges as a promising drug candidate warranting further investigation.
Farnaz Zahedifard, Meenakshi Bansal, Neha Sharma, Sumit Kumar, Siqi Shen, Priyamvada Singh, Brijesh Rathi, and Martin Zoltner
Public Library of Science (PLoS)
Pharmacophores such as hydroxyethylamine (HEA) and phthalimide (PHT) have been identified as potential synthons for the development of compounds against various parasitic infections. In order to further advance our progress, we conducted an experiment utilising a collection of PHT and HEA derivatives through phenotypic screening against a diverse set of protist parasites. This approach led to the identification of a number of compounds that exhibited significant effects on the survival of Entamoeba histolytica, Trypanosoma brucei, and multiple life-cycle stages of Leishmania spp. The Leishmania hits were pursued due to the pressing necessity to expand our repertoire of reliable, cost-effective, and efficient medications for the treatment of leishmaniases. Antileishmanials must possess the essential capability to efficiently penetrate the host cells and their compartments in the disease context, to effectively eliminate the intracellular parasite. Hence, we performed a study to assess the effectiveness of eradicating L. infantum intracellular amastigotes in a model of macrophage infection. Among eleven L. infantum growth inhibitors with low-micromolar potency, PHT-39, which carries a trifluoromethyl substitution, demonstrated the highest efficacy in the intramacrophage assay, with an EC50 of 1.2 +/- 3.2 μM. Cytotoxicity testing of PHT-39 in HepG2 cells indicated a promising selectivity of over 90-fold. A chemogenomic profiling approach was conducted using an orthology-based method to elucidate the mode of action of PHT-39. This genome-wide RNA interference library of T. brucei identified sensitivity determinants for PHT-39, which included a P-type ATPase that is crucial for the uptake of miltefosine and amphotericin, strongly indicating a shared route for cellular entry. Notwithstanding the favourable properties and demonstrated efficacy in the Plasmodium berghei infection model, PHT-39 was unable to eradicate L. major infection in a murine infection model of cutaneous leishmaniasis. Currently, PHT-39 is undergoing derivatization to optimize its pharmacological characteristics.
Monika Chaudhary, Priyamvada Singh, Gajendra Pratap Singh, and Brijesh Rathi
American Chemical Society (ACS)
Carbon dots (CDs) have drawn attention due to their enticing physical, chemical, and surface properties. Besides, good conductivity, low toxicity, environmental friendliness, simple synthetic routes, and comparable optical properties are advantageous features of CDs. Further, recently, CDs have been explored for biological systems, including plants. Among biological systems, only plants form the basis for sustainability and life on Earth. In this Review, we reviewed suitable properties and applications of CDs, such as promoting the growth of agricultural plants, disease resistance, stress tolerance, and target transportation. Summing up the available studies, we believe that the applications of CDs are yet to be explored significantly for innovation and technology-based agriculture.
Monika Kumari, Bhupender S. Chhikara, Priyamvada Singh, and Brijesh Rathi
Sumit Kumar, R Bhuvaneshwari, Sejal Jain, Shweta Nirwan, Zainab Fatima, Dharmender Kumar, Bhupendra S. Chhikara, Brijesh Rathi, and Poonam
Bentham Science Publishers Ltd.
Abstract: Synthetic pesticides, crucial compounds for agricultural production, degrade quickly and damage the environment, hence solutions for their decreased usage or formulations with prolonged efficacy at low dosages are needed. Nanotechnology for nanosized formulations may reduce pesticide adverse effects. Nano-encapsulated pesticides made from nanocapsules, nanoemulsions, micelles, and nanogels outperform traditional pesticides with minimum environmental impact. Nanopesticides allowed target-based administration to decrease leaching and drainage into water bodies, and lower pesticide active component dosages. Nanocapsules with a core-shell configuration and a pesticide in the core are the most advantageous nanomaterials. Nanocapsules shield the active component. Stimuli-responsive nanocapsules may limit pesticide release by responding to pH, temperature, light, enzyme, or redox reactions. Toxicity prevents their use. This review discusses the latest developments in nanocapsule fabrication methods, their relevance, contemporary synthetic approaches to developing pesticide-loaded nanocapsules, and the features of these nanocomposites, with an emphasis on sustainable agricultural applications.
Manoj Kumar, Shalini Verma, Mukul Sharma, Poonam, and Brijesh Rathi
Wiley
AbstractBenzo‐fused five‐membered N/O/S heterocyclic compounds, such as indole, benzofuran, and benzothiophene, possessing a single heteroatom, have important applications in medicinal chemistry, agrochemistry, and material chemistry. Metal‐catalysed reactions are well‐established synthetic pathways for the formation of C−X bonds, enabling the direct synthesis of heterocycles. This approach offers advantages over traditional methods, such as fewer steps, increased atom economy, low catalyst loading, regioselectivity, and stereoselectivity. Due to their widespread use in the pharmaceutical industry, the formation of C−N, C−O, and C−S bonds has gained significant attention. This article focusses on the metal‐catalysed synthesis and corresponding mechanistic approaches for N/O/S‐heterocycles, particularly indole, benzofuran, and benzothiophene, reviewing the progress of the past five years and discussing unexplored future opportunities.
Miklós Bege, Vigyasa Singh, Neha Sharma, Nóra Debreczeni, Ilona Bereczki, Poonam, Pál Herczegh, Brijesh Rathi, Shailja Singh, and Anikó Borbás
Springer Science and Business Media LLC
AbstractDrug-resistant Plasmodium falciparum (Pf) infections are a major burden on the population and the healthcare system. The establishment of Pf resistance to most existing antimalarial therapies has complicated the problem, and the emergence of resistance to artemisinin derivatives is even more concerning. It is increasingly difficult to cure malaria patients due to the limited availability of effective antimalarial drugs, resulting in an urgent need for more efficacious and affordable treatments to eradicate this disease. Herein, new nucleoside analogues including morpholino-nucleoside hybrids and thio-substituted nucleoside derivatives were prepared and evaluated for in vitro and in vivo antiparasitic activity that led a few hits especially nucleoside-thiopyranoside conjugates, which are highly effective against Pf3D7 and PfRKL-9 strains in submicromolar concentration. One adenosine derivative and four pyrimidine nucleoside analogues significantly reduced the parasite burden in mouse models infected with Plasmodium berghei ANKA. Importantly, no significant hemolysis and cytotoxicity towards human cell line (RAW) was observed for the hits, suggesting their safety profile. Preliminary research suggested that these thiosugar-nucleoside conjugates could be used to accelerate the antimalarial drug development pipeline and thus deserve further investigation.
Ronaldo Celerino da Silva, Suelen Cristina de Lima, Wendell Palôma Maria dos Santos Reis, Jurandy Júnior Ferraz de Magalhães, Ronaldo Nascimento de Oliveira Magalhães, Brijesh Rathi, Alain Kohl, Marcos André Cavalcanti Bezerra, and Lindomar Pena
Public Library of Science (PLoS)
The coronavirus disease 2019 (COVID-19) pandemic has resulted in global shortages in supplies for diagnostic tests, especially in the developing world. Risk factors for COVID-19 severity include pre-existing comorbidities, older age and male sex, but other variables are likely play a role in disease outcome. There is indeed increasing evidence that supports the role of host genetics in the predisposition to COVID-19 outcomes. The identification of genetic factors associated with the course of SARS-CoV-2 infections relies on DNA extraction methods. This study compared three DNA extraction methods (Chelex®100 resin, phenol-chloroform and the QIAamp DNA extraction kit) for COVID-19 host genetic studies using nasopharyngeal samples from patients. The methods were compared regarding number of required steps for execution, sample handling time, quality and quantity of the extracted material and application in genetic studies. The Chelex®100 method was found to be cheapest (33 and 13 times cheaper than the commercial kit and phenol-chloroform, respectively), give the highest DNA yield (306 and 69 times higher than the commercial kit and phenol-chloroform, respectively), with the least handling steps while providing adequate DNA quality for downstream applications. Together, our results show that the Chelex®100 resin is an inexpensive, safe, simple, fast, and suitable method for DNA extraction of nasopharyngeal samples from COVID-19 patients for genetics studies. This is particularly relevant in developing countries where cost and handling are critical steps in material processing.
Anjli Hooda, Devender Singh, Anuj Dalal, Kapeesha Nehra, Sumit Kumar, Rajender Singh Malik, Brijesh Rathi, and Parvin Kumar
Elsevier BV
Zhao Wang, Prem Prakash Sharma, Brijesh Rathi, Minghui Xie, Erik De Clercq, Christophe Pannecouque, Dongwei Kang, Peng Zhan, and Xinyong Liu
American Chemical Society (ACS)
In the current landscape of antiretroviral options, there remains an urgent need for novel non-nucleoside reverse transcriptase inhibitors (NNRTIs) with improved resistance profiles and safety properties. Herein, a series of novel tetrahydropyrido[4,3-d]pyrimidine derivatives were discovered utilizing the "escape from flatland" strategy. The most potent inhibitor 10c was endowed with broad-spectrum antiviral activity and improved resistance profiles against NNRTI-resistant variants compared to efavirenz and etravirine. Molecular simulations were investigated to furnish insights into the biological results. Drug-likeness assessment showed that 10c exhibited desirable physicochemical properties and in vitro metabolic stability. Notably, lower cytochrome P450 inhibition and human ether-à-go-go-related gene blockade liability were observed for 10c than those for etravirine and rilpivirine. Besides, 10c was characterized by excellent in vivo safety properties without acute/subacute toxicity and organ pathological damage. Overall, our multiparameter optimization campaign led to the identification of 10c with excellent antiviral activities and favorable drug-like profiles that could serve as an ideal drug candidate for further development.
Renata Maria Costa Souza, Lilian Maria Lapa Montenegro Pimentel, Laryssa Kathleen Mendonça Ferreira, Valéria Rêgo Alves Pereira, Aline Caroline Da Silva Santos, Willyenne Marília Dantas, Carla Jasmine Oliveira Silva, Ramayana Morais De Medeiros Brito, José Lucas Andrade, Valter Ferreira De Andrade-Neto,et al.
Elsevier BV
Anuj Dalal, Kapeesha Nehra, Anjli Hooda, Devender Singh, Parvin Kumar, Sumit Kumar, Rajender Singh Malik, and Brijesh Rathi
Elsevier BV
Anjli Hooda, Devender Singh, Kapeesha Nehra, Anuj Dalal, Sumit Kumar, Rajender Singh Malik, Brijesh Rathi, and Parvin Kumar
Elsevier BV
Sumit Kumar, Dharna Yadav, Divya Singh, Kriti Shakya, Brijesh Rathi, and Poonam
Wiley
Junin virus consists of ribonucleic acid as the genome and is responsible for a rapidly changing tendency of the virus. The virus is accountable for ailments in the human body and causes Argentine Haemorrhagic Fever (AHF). The infection is may be transmitted through contact between an infected animal/host and a person, and later between person to person. Prevention of outbreaks of AHF in humans can be a tough practice, as their occurrence is infrequent and unpredictable. In this review, recent information from the past 5 years available on the Junin virus including the risk of its emergence, infectious agents, its pathogenesis in humans, available diagnostic and therapeutic approaches, and disease management has been summarised. Altogether, this article would be highly significant in understanding the mechanistic basis behind virus interaction and other processes during the life cycle. Currently, no specific therapeutic options are available to treat the Junin virus infection. The information covered in this review could be important for finding possible treatment options for Junin virus infections.
Anjani, Sumit Kumar, Brijesh Rathi, and Poonam
Royal Society of Chemistry (RSC)
The role of functional group in discovery of Nirmatrelvir is valuable and interesting for development of various inhibitors against viral diseases.
Babban Jee, Prem Prakash Sharma, Vijay Kumar Goel, Sanjay Kumar, Yogesh Singh, and Brijesh Rathi
Bentham Science Publishers Ltd.
Background: DosR is a transcriptional regulator of Mycobacterium tuberculosis (MTB), governing the expression of a set of nearly 50 genes that is often referred to as ‘dormancy regulon’. The inhibition of DosR expression by an appropriate inhibitor may be a crucial step against MTB. Objective: We targeted the DosR with natural metabolites, ursolic acid (UA) and carvacrol (CV), using in silico approaches. Methods: The molecular docking, molecular dynamics (MD) simulation for 200 ns, calculation of binding energies by MM-GBSA method, and ADMET calculation were performed to evaluate the inhibitory potential of natural metabolites ursolic acid (UA) and carvacrol (CV) against DosR of MTB. Results: Our study demonstrated that UA displayed significant compatibility with DosR during the 200 ns timeframe of MD simulation. The thermodynamic binding energies by MM-GBSA also suggested UA conformational stability within the binding pocket. The SwissADME, pkCSM, and OSIRIS DataWarrior showed a drug-likeness profile of UA, where Lipinski profile was satisfied with one violation (MogP > 4.15) with no toxicities, no mutagenicity, no reproductive effect, and no irritant nature. Conclusion: The present study suggests that UA has the potency to inhibit the DosR expression and warrants further investigation on harnessing its clinical potential.
Arbaz Sujat Shaikh, Aaftaab Sethi, Priyanka N. Makhal, Brijesh Rathi, and Venkata Rao Kaki
Informa UK Limited
Matrix Metalloproteinases-9 (MMP-9) is one of the important targets that play a vital role in various diseases such as cancer, Alzheimer's, arthritis, etc. Traditionally, MMP-9 inhibitors have been unable to achieve selectivity to get around this target; thereby, novel mechanisms such as inhibition of activated MMP-9 zymogen (pro-MMP-9) have been discovered. The JNJ0966 was one of the few compounds that attained the requisite selectivity by inhibiting the activation of MMP-9 zymogen (pro-MMP-9). Since JNJ0966, no other small molecules have been identified. Herein, extensive in silico studies were called upon to bolster the prospect of exploring potential candidates. The key objective of this research is to identify the potential hits from the ChEMBL database via molecular docking and dynamics approach. Protein with PDB ID: 5UE4, having a unique inhibitor in an allosteric binding pocket of MMP-9, was chosen for the study. Structure-based virtual screening and MMGBSA binding affinity calculations were performed, and five potential hits were finalized. Detailed analysis of the best-scoring molecules was performed with ADMET analysis and molecular dynamics (MD) simulation. All five hits outperformed JNJ0966 in the docking assessment, ADMET analysis, and molecular dynamics simulation. Accordingly, our research findings imply that these hits can be investigated for in vitro and in vivo studies against proMMP9 and might be explored as potential anticancer drugs. The outcome of our research might contribute in expediting the exploration of drugs that inhibits proMMP-9.Communicated by Ramaswamy H. Sarma.
Himanshi Sharma, Manoj Kumar, Aaftaab Sethi, Poonam, and Brijesh Rathi
Royal Society of Chemistry (RSC)
Herein, we report a metal/additive-free protocol for the activation of nitrile towards nucleophilic addition and subsequent annulation under an aqueous medium for the first time.
Sujata Maurya, Rashi Srivastava, Saniya Arfin, Susan Hawthorne, Niraj Kumar Jha, Kirti Agrawal, Sibi Raj, Brijesh Rathi, Arun Kumar, Riya Raj,et al.
Future Medicine Ltd
Diagnosis and treatment of lung diseases pose serious challenges. Currently, diagnostic as well as therapeutic methods show poor efficacy toward drug-resistant bacterial infections, while chemotherapy causes toxicity and nonspecific delivery of drugs. Advanced treatment methods that cure lung-related diseases, by enabling drug bioavailability via nasal passages during mucosal formation, which interferes with drug penetration to targeted sites, are in demand. Nanotechnology confers several advantages. Currently, different nanoparticles, or their combinations, are being used to enhance targeted drug delivery. Nanomedicine, a combination of nanoparticles and therapeutic agents, that delivers drugs to targeted sites increases the bioavailability of drugs at these sites. Thus, nanotechnology is superior to conventional chemotherapeutic strategies. Here, the authors review the latest advancements in nanomedicine-based drug-delivery methods for managing acute and chronic inflammatory lung diseases.
Prem Prakash Sharma, Shakshi Bhardwaj, Aaftaab Sethi, Vijay K. Goel, Maria Grishina, Poonam, and Brijesh Rathi
Elsevier BV