BITS Faculty Publications
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Item Plant essential oils as potent antimicrobials(Springer, 2024-01) Paul, Atish TulshiramAntimicrobial resistance (AMR) is spreading at an alarming rate, reducing the effectiveness of antibiotics and producing undesirable results such as increased mortality and significant economic loss. Public health is seriously threatened by this global problem, which restricts our capacity to treat common infections and increases risk for vulnerable groups. To address this expanding issue, a novel and effective antimicrobial agent or treatment strategy is needed. Essential oils represent an important source of a diverse range of bioactive constituents with potent antimicrobial activity. Wider acceptance due to its traditional use, lower toxicity, and ability to target multiple determinants of resistance makes essential oils a potent candidate for effectively tackling AMR and eradicating drug-resistant pathogens. Essential oil-loaded nanomaterials have also shown improved efficacy in treating antimicrobial resistance due to increased bioavailability, stability, and solubility and reduced degradation of the active principles of essential oils. Furthermore, combining essential oils with antibiotics has a synergistic impact, helping to revitalize an otherwise depleted antibiotic arsenal. This chapter gives a comprehensive summary of the antibacterial properties of essential oils and their active principles. The chapter also highlights the major bacterial AMR-determinants targeted by plant essential oils besides discussing the successful experiments on the combination of essential oils with antibiotics and nanomaterials for combating drug-resistant microbes.Item Discovery of novel chromone and acrylate-based pancreatic lipase inhibitors: Molecular modelling, synthesis, and in vitro evaluation for the treatment of obesity(Wiley, 2024-01) Paul, Atish TulshiramBy the optimization of previously established pancreatic lipase (PL) inhibitory lead, we have developed novel chromone-containing analogues with embedded acrylate fragment as potential PL inhibitors. The analogues were designed by considering the structural features required for binding at the active site of PL enzyme with the utilization of molecular docking study. An optimized synthetic scheme was utilized for the synthesis of designed analogues of prototypes 1&2. Through in vitro PL inhibitory screening, three analogues namely, 5fj, 5gj and 9a were identified as potent PL inhibitory leads with IC50 values of 4.92, 4.23 and 3.32 μM, respectively. The protein binding of analogue 9a was analysed by fluorescence quenching study and it was found to bind at one binding site with a binding constant of 1.93 × 105 L mol−1. Analogue 9a also exhibited a competitive inhibitory mechanism with Ki value of 1.601 μM. In future, the potent lead 9a can be optimized to get a comparable or more potential PL inhibitory activity than marketed drugs.Item Computational insights into human UCP1 activators through molecular docking, MM-GBSA, and molecular dynamics simulation studies(Elsevier, 2024-12) Paul, Atish TulshiramThe prevalence of obesity is rapidly increasing worldwide. Brown adipose tissue activates uncoupling protein 1 (UCP1) to generate heat through bypassing ATP synthesis, offering a potential target for obesity treatment. Targeting UCP1 activation to induce thermogenesis through small molecules presents a promising approach for obesity management. In this study, molecular docking of UCP1 activators, using 2,4-dinitrophenol (DNP) as a reference ligand (PDB ID: 8J1N, docking score: −5.343 kcal/mol), identified seven top-scoring compounds: naringin (-7.284 kcal/mol), quercetin (-6.661 kcal/mol), salsalate (-6.017 kcal/mol), rhein (-5.798 kcal/mol), mirabegron (-5.535 kcal/mol), curcumin (-5.479 kcal/mol), and formoterol (-5.451 kcal/mol). Prime MM-GBSA calculation of the top-scored molecule (i.e., naringin) in the docking study showed ΔGBind of −70.48 kcal/mol. Key interactions of these top 7 activators with UCP1 binding pocket residues Trp280, Arg276, Glu190, Arg83, and Arg91 were observed. Molecular dynamics simulations performed for 100 ns confirmed complex stability, with RMSD values below 6 Å. Additionally, most activators showed favorable intestinal absorption (>90 %) and lipophilicity (LogP 2–4), with pKa values supporting their pharmacological potential as UCP1-targeting therapeutics for obesity. These findings provide a foundation for designing potent UCP1 activators by integrating docking scores, interaction profiles, statistical profiles from MD simulations, and physicochemical assessments to develop effective anti-obesity therapies.Item Synthetic pancreatic lipase inhibitors in obesity treatment: current updates on in silico design, synthesis, bioactivity, and SAR(RSC, 2025-09) Paul, Atish TulshiramTaking a stand against obesity is an urgent priority, as it significantly impacts both the global economy and public health. Synthetic pancreatic lipase (PL) inhibitors represent one of the most effective therapeutics in the management of obesity. PL is a triacylglycerol acyl hydrolase from the family of serine hydrolases that play a key role in the hydrolysis of dietary fat into monoglycerides and fatty acids. Further, fatty acids get deposited in adipose tissue, which progressively results in weight gain. Over the last decade, various new drugs have been studied; however, orlistat still remains the first-line FDA-approved drug for obesity management. However, long-term use of orlistat can lead to serious health complications, including liver toxicity, osteoporosis, and gastrointestinal issues. Notably, the formation of an irreversible covalent bond of the β-lactone moiety of orlistat with the active serine site of HPL and PPL enzyme has been considered to be responsible for these complications. A deeper understanding of the crystal structure of HPL indicates that repositioning the hydrophobic lid domain, also known as the flap, opens access for designed inhibitors to interact with the active site residues: Ser152, His263, and Asp176. Additionally, predicting the mode of inhibition and the inhibition constant (Ki) value through enzyme kinetic study is helpful. This review presents a comprehensive overview of the in silico design, synthetic strategies, in vitro assays using human (HPL) and porcine (PPL) enzymes, in vivo activity, and structure–activity relationship (SAR) studies of synthetic PL inhibitors reported since 2014, aimed at the development of anti-obesity agents. Additionally, we propose the challenges to overcome and a potential path for future development in this field.Item Quantitative UV spectrophotometric analysis of teriflunomide and quercetin in dual drug-loaded transferosomes using the absorption factor method(Springer, 2025-05) Jindal, Anil B.; Paul, Atish TulshiramThe current research focused on establishing a method for concurrently measuring teriflunomide (TFD) and querectin (QCN) accurately, precisely, and with simplicity. This method aims to be suitable for routine analysis purposes. The goal is to effectively utilize this combination effectively in the treatment of rheumatoid arthritis (RA) through a topical delivery approach. To date, there have been no reported UV-based methods for simultaneous estimation of TFD and QCN. The quantification was performed using the absorption factor method for multicomponent analysis. The developed method underwent validation in accordance with the guidelines set by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). The validated method demonstrated linearity within the concentration range of 2.0 to 12.0 μg/mL for both substances, exhibiting a regression coefficient of > 0.990. The developed method validated for accuracy and precision, demonstrating a recovery rate within the range and precision with an RSD of less than 2 % for both inter and intra-day measurements. Moreover, the developed method was effectively utilized for quantification in the prepared transferosomes using absorption factor method. The greenness of the proposed methods was assessed, showing their minimal environmental impact and low level of toxicity to the environment.Item Histone demethylase inhibitors: developmental insights and current status(Taylor & Francis, 2025-08) Paul, Atish Tulshiram; Jadhav, Hemant R.The discovery of histone demethylases (HDMs) has greatly advanced our epigenetic understanding, particularly their role in post-translational modifications of histones. HDMs regulate cellular functions, such as X chromosome inactivation, differentiation, cell-based aging, and deoxyribonucleic acid (DNA) damage repair. Although crucial for regulating genetic expression, post-translational modifications have been implicated in developing several diseases. The discovery and development of inhibitors targeting HDMs have emerged as an active and rapidly expanding research field over the last few years. This review attempts to collate the available information on different isoforms of HDMs, substrate selectivity, and involvement in various biological functions. Also, the existing as well as emerging HDM inhibitors, especially inhibitors of histone lysine (K) demethylase 1 (KDM1) and the jumonji-C (JmjC) family demethylases (KDM 2–8), are reported along with analysis on insights for the future development of HDM inhibitors.Item Unveiling the potential of naturally occurring rosmarinic acid inspired analogues as pancreatic lipase inhibitors: In silico, in vitro and in vivo evaluation as anti-obesity agents(Elsevier, 2025-12) Paul, Atish TulshiramPancreatic Lipase (PL) is a prime enzyme responsible for the digestion of dietary fat and is considered a safer and more efficient target for managing obesity. Orlistat is the only approved drug for the long-term management of obesity. In this study, using a molecular docking study, various inhibitors were designed via structural optimization of one of the moderately active natural products, namely, rosmarinic acid. A total of 17 acrylate-linked chromone analogues were synthesized, followed by structure elucidation via NMR spectroscopy and HR-MS. To confirm the stereochemistry of the analogues, a single-crystal XRD spectroscopy was performed for analogue 5ab. Among all the synthesized analogues, six analogues were found to exhibit IC50 values in the range of 1.24–2.76 µM. The analogue 5gb was the most potent among the series with IC50 of 1.24 ± 0.296 µM. The enzyme kinetics study revealed a competitive inhibitory mechanism, with Ki values of 0.554 and 0.488 for 5gb and orlistat, respectively. The number of binding sites (n) and binding constant values were obtained through a fluorescence quenching study and found to be 0.57 and 2.97 × 105 L mol−1, respectively, confirming the single binding site of analogue 5gb in the PL enzyme. Through in vivo screening, 5gb was found to exhibit significant weight reduction and normalization of the serum parameters (triglycerides, total cholesterol, HDL, and LDL cholesterol) at a dose of 20 mg/kg. Through a faecal triglyceride quantification study, the PL inhibitory mechanism was confirmed. Further, the histopathological changes (that occurred in obese animals) in liver and adipose tissue were normalized in the case of 5gb treatment groups. Thus, 5gb possessed a comparable anti-obesity activity to that of orlistat.Item Synthesis, molecular modelling and biological evaluation of novel benzyloxy substituted indolyl oxoacetamides as potent pancreatic lipase inhibitors(Springer, 2025-08) Paul, Atish TulshiramA series of 21 indolyl oxoacetamide analogues with benzyloxy-substituents were designed, synthesized and characterized using 1H NMR (Nuclear Magnetic Resonance), 13C NMR, and HRMS (High Resolution Mass Spectrometry) analysis. All the analogues were tested for inhibitory activity against pancreatic lipase. Two analogues, 9f and 10f, exhibited significant activity (IC50 of 2.89 and 2.50 µM, respectively), comparable to the standard drug, orlistat (IC50 = 0.99 µM). The potent analogues 10f and 9f exhibited significant binding affinity for pancreatic lipase (-170.222 kcal mol− 1 and − 153.547 kcal mol− 1). Additionally, both the potent analogues exhibited crucial interaction with Ser 152 and His 263 residues in the PL active site via hydrogen bonding. Molecular dynamics (MD) simulation was performed on the ligand-receptor complex of potent analogue (10f) for 200 ns. The molecule was stabilized by extending the π-π interactions with Phe 77 and Phe 215 of the active site lid domain due to benzyloxy substitution. Toxicity profile prediction indicated that all the analogues were non-hepatotoxic, unlike orlistat.Item Discovery of thiazolidinedione-based pancreatic lipase inhibitors as anti-obesity agents: synthesis, in silico studies and pharmacological investigations(Taylor & Francis, 2024-02) Paul, Atish TulshiramA series of new 2,5-disubstituted arylidene derivatives of thiazolidinedione (16a-e, 17a-d, 18a-c) designed using molecular hybridization approach were synthesized, structurally characterized, and explored for their anti-obesity potential via inhibition of Pancreatic Lipase (PL). Compound 18a presented the most potent PL inhibitory activity with IC50 = 2.71 ± 0.31 µM, as compared to the standard drug, Orlistat (IC50 = 0.99 µM). Kinetic study revealed reversible competitive mode of enzyme inhibition by compound 18a with an inhibitory constant value of 1.19 µM. The most promising compound 18a revealed satisfactory binding mode within the active site of the target protein (human PL, PDB ID: 1LPB). Also, MM/PBSA binding free energy and molecular dynamics (MD) simulation analysis were performed for the most promising compound 18a, which showed potent inhibition according to the results of in vitro studies. Furthermore, a stable conformation of the 1LPB-ligand suggested the stability of this compound in the dynamic environment. The ADME and toxicity analysis of the compounds were examined using web-based online platforms. Results of in vivo studies confirmed the anti-obesity efficacy of compound 18a, wherein oral treatment with compound 18a (30 mg/kg) resulted in a significant reduction in the body weight, BMI, Lee index, feed intake (in Kcal), body fat depots and serum triglycerides. Compound 18a significantly decreased the levels of serum total cholesterol (TC) to 128.6 ± 0.59 mg/dl and serum total triglycerides (TG) to 95.73 ± 0.67 mg/dl as compared to the HFD control group. The present study identified disubstituted TZD derivatives as a new promising class of anti-obesity agents.Item Integrated metabolomic, molecular, and morphological insights into the degradation of polychlorinated biphenyls (PCB) by priestia megaterium mapb-27(ACS, 2025-10) Paul, Atish Tulshiram; Jha, Prabhat NathPolychlorinated biphenyls (PCBs) are persistent organic pollutants that cause profound deleterious effects on the environment and human health. Exposure to PCBs and biphenyl can induce changes in cellular metabolite levels. However, metabolic responses to utilize and adapt to PCBs are not well understood. Therefore, this study meticulously examined the PCB degradation potential, gene expression, and metabolic responses of Priestia megaterium MAPB-27 exposed to biphenyl. MAPB-27 showed growth and chemotaxis toward PCB degradation intermediates such as biphenyl, dihydroxy biphenyl, benzoate, and catechol. We employed GC-MS/MS to elucidate disparities in the main metabolic pathways in the biphenyl-exposed MAPB-27 through variations in metabolite composition and PCB biodegradation, while Field-emission scanning electron microscopy (FESEM) was used to study cell morphology. GC-MS/MS analysis highlighted the degradation of trichlorobiphenyl, tetrachlorobiphenyl, pentachlorobiphenyl, and hexachlorobiphenyl by P. megaterium MAPB-27, exhibiting 92.5, 62.9, 3.7, and 2.4%, respectively. GC-MS/MS analysis identified 4-dihydroxy-2-oxo-valerate, benzoic acid, and 2,3-dihydroxybenzoic acid as the major degradative metabolites in MAPB-27. MAPB-27 extract also contains metabolites with a wide range of direct industrial applications, such as poly(3-hydroxybutyrate) (3-hydroxybutyrate), a biobased organic acid (3-hydroxypropionoic acid), and antibacterial and antifungal compounds (phenyllactic acid, 4-hydroxyphenyllactic acid, and β-sitosterol). Glyoxylate and dicarboxylate metabolism and fatty acid biosynthesis were observed to be the active metabolisms in MAPB-27 grown in biphenyl-supplemented Minimal Medium. Overall, the results of this study provided important insights into microbial adaptation to biphenyl and the biodegradation of PCB. Thus, the P. megaterium MAPB-27 strain can be used for the development of efficient PCB biodegradation strategies and for the exploration of industrial applications.