Browsing by Author "Diksha Katiyar"

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Anti-metastatic cancer potential of 4H-chromene derivatives targeting JNK in Scribble knockdown induced epithelial cancer model: In vivo and in silico studies
(Academic Press Inc., 2025) Vaishali Raghuvanshi; Jyotsna Singh; Saurabh Sharma; Ray Jay Butcher; Saripella Srikrishna; Diksha Katiyar
Building on our previous work on the synthesis of a series of 4H-chromene derivatives, we report herein for the first time the in vivo and in silico studies of ten chromene derivatives 5a-j as potential anti-metastatic cancer agents targeting through c-Jun N-terminal kinase (JNK). Compounds 5a-j were resynthesized using the protocol previously reported by our research group. Out of these, 5c, 5f-h and 5j showed good anti-metastatic cancer activity in Drosophila in vivo model, with 5f being the most active. It exhibited 27% rescue in metastatic cancer induced pupal lethality, whereas the standard drug sorafenib showed no rescue. Furthermore, 5f has significantly downregulated JNK and the metastasis promoting marker enzyme, matrix metalloproteinase-1 (MMP1) expression in Scribble (Scrib) knockdown induced Drosophila cancer tissues. In silico studies of all the compounds, 5a-j, demonstrated strong binding affinity with Drosophila JNK protein (PDB ID: 5AWM). Additionally, comparison of the docking positions of 5f in the 5AWM and human JNKs (PDB IDs: 1UKH and 3E7O) binding sites revealed a high degree of homology between them with respect to the similar set of amino acids interacting with the ligand. Compounds 5a-j also exhibited favourable pharmacokinetic properties with drug-like characteristics, as predicted by SwissADME analysis. The crystal structure of 5f was determined for the first time using single-crystal X-ray diffraction (SC-XRD) analysis. It crystallizes in a monoclinic crystal system with the space group P21/c, providing valuable insights into its structural features and molecular arrangement. The present findings strongly suggest that the chromene derivatives, represented by compound 5f, hold promise as potential anticancer agents targeting the metastatic stage in various epithelial cell-derived cancers. © 2025 Elsevier Inc.
Benzopyran, Benzamidocoumarin, Phenylpyrrolidine, and Barbituric Acid Derivatives as Potential Actives Targeting Endonuclease VIII-2 (Nei2) of Mycobacterium Tuberculosis
(John Wiley and Sons Inc, 2025) Urvashi Goyal; Tabish M. Rehman; Darin Mansor Mathkor; Diksha Katiyar; Abha Bishnoi; Vineeta K. Singh; B. N. Mishra; Shafiul Haque
Emerging drug resistance in Mycobacterium tuberculosis (M. tuberculosis) has forced us to find novel drug targets. Endonuclease VIII 2 or DNA base excision repair glycosylase, is such an enzyme. Newly synthesized inhibitors derived from benzopyran, benzamidocoumarin, 5-oxo-1-phenylpyrrolidine-3-carboxylic acid, their Claisen products, and barbituric acid were evaluated for their potential to inhibit M. tuberculosis Endonuclease VIII 2. Endonuclease VIII 2 (Nei2) structure was modeled and analyzed. An in-house library of 72 synthetic compounds was prepared and analyzed for drug-likeness and ADMET properties. Finally, 67 compounds were screened against the active site of Nei2, and on the basis of docking energy, compound 1s [ethyl (4R)-4-(3,5-dichloro-2-hydroxyphenyl)-5,7-dihydroxy-2-methyl-4H-1-benzopyran-3-carboxylate] was identified as the most promising drug candidate. The binding energy (ΔG) and binding affinity (Ka) of 1s toward the active site of Nei2 were −9.8072 kcal mol−1 and 1.56 × 107m−1, respectively. The corresponding dissociation constant (Kd) value of compound 1s was estimated to be 64.1 nM. Compound 1s formed hydrogen bonds and hydrophobic interactions with the key active site residues of Nei2 such as Met1, Pro2, Glu3, Lys51, Leu66, Met68, Val165, and Tyr166. Molecular dynamics simulations suggested the formation of a stable Nei2-1s complex. The analysis of compound 1s for drug-likeness and ADMET properties established it as a potential drug against TB, pending experimental validation. © 2025 Wiley-VCH GmbH.
Biotransformation of newly synthesized coumarin derivatives by Candida albicans as potential antibacterial, antioxidant and cytotoxic agents
(Elsevier Ltd, 2019) Ambreen; Shafiul Haque; Vineeta Singh; Diksha Katiyar; Mohd Tariq Ali Khan; Vikash Tripathi; Hesham El Enshasy; Mukesh Pasupuleti; Bhartendu Nath Mishra
In this study, one bioactive coumarin analog was obtained as a result of biotransformation of three inactive coumarin derivatives by free cells of Candida albicans. The bioactive analog was purified by Column chromatography and HPLC. The presence of coumarin moiety in the biotrasformed product was confirmed by λmax at 350–400 nm and FT-IR spectrum. The structure of the purified compound established by LC–MS and 1H NMR suggests the chances of biotransformation of 7-(3-(Cyclopropylamino)-2-hydroxypropoxy)-4-methyl-2H-chromen-2-one (MW 289 Da) into 7-(3-Cyclopropylamino-2-hydroxy-propoxy)-4-methoxymethyl-chromen-2-one or 7-(3-Cyclopropylamino-2-methoxy-propoxy)-4-hydroxymethyl-chromen-2-one as a main product (MW 318 Da). The extra peak of 332 Da in LC–MS further confirms the presence of small proportion of 7-(3-Cyclopropylamino-2-methoxy-propoxy)-4-methoxymethyl-chromen-2-one apart from the main product. Oxidation followed by methylation reaction might be responsible for this conversion. The biotransformed product showed antimicrobial activity against Bacillus pumilus, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae and Salmonella typhi followed by decent antioxidant activity (6.756 μg IC50). The efficacy of coumarin-analog on cellular proliferation was found at 40 μM concentration against human breast cancer MDA-MB-231 cells in MTT assay, which is insignificant against normal breast tissue MCF-10A cells at the same concentration. These findings suggest the potential use of C. albicans for achieving pharmacologically active coumarin analogs showing antibacterial, antioxidant and cytotoxic activity. © 2019
Combined experimental and theoretical studies on 4-(2-hydroxy-3-morpholin-4-yl-propoxy)-chromen-2-one
(World Scientific Publishing Co. Pte Ltd, 2016) Priyanka; Sanjay Kumar Srivastava; Diksha Katiyar
The FTIR, UV-Vis and NMR spectra of 4-(2-hydroxy-3-morpholin-4-yl-propoxy)-chromen-2-one (4-HMPC) have been recorded and analyzed. The optimized geometry and harmonic vibrational frequencies of 4-HMPC were obtained by the Hartree-Fock (HF) and density functional theory (DFT) using B3LYP functional with 6-311++G basis set. The 1H and 13C NMR chemical shifts were calculated by the GIAO method in chloroform. The absorption spectra of 4-HMPC were computed in ethanol and water solutions using TD-B3LYP/6-311++G(d,p) approach. The correlation of theoretical and experimental results provides a detailed description of the structural and physicochemical properties of the molecule. The results obtained from the studies of HOMO and LUMO were used to calculate the conceptual-DFT-based global reactivity descriptors such as electronic chemical potential, electronegativity, chemical hardness, global softness and electrophilicity index of the compound. © 2016 World Scientific Publishing Company.
Design, synthesis and biological evaluation of some new coumarin derivatives as potential antimicrobial agents
(Bentham Science Publishers B.V., 2015) Lav Kumar Singh; Priyanka; Vineeta Singh; Diksha Katiyar
A series of 4-methyl-7-O-substituted coumarins (3-12) was synthesized and evaluated for in vitro antimicrobial activity against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), four Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Proteus vulgaris) and three fungal strains (Candida albicans, Cryptococcus terreus and Saccharomyces cerevisiae) by two-fold serial dilution technique. The results of bioactive assay showed that some of the synthesized coumarins displayed comparable or even better antibacterial and antifungal activities against tested strains in comparison with reference drugs erythromycin, novobiocin and amphotericin B. Compound 9 showed potent antimicrobial activities against seven of the nine microbial strains examined in this study with MIC values ranging between 1.09 and 25 μg/mL and was the most active compound of the series. The present work also describes the effect of substituent on bioactivity. © 2015 Bentham Science Publishers.
Dyshomeostasis of Iron and Its Transporter Proteins in Cypermethrin-Induced Parkinson’s Disease
(Springer, 2023) Nidhi Sachan; Neha Tiwari; Devendra Kumar Patel; Diksha Katiyar; Saripella Srikrishna; Mahendra Pratap Singh
The etiology of Parkinson’s disease (PD) is highly complex and is still indefinable. However, a number of studies have indicated the involvement of pesticides and transition metals. Copper, magnesium, iron, and zinc have emerged as important metal contributors. Exposure to pesticides causes an accumulation of transition metals in the substantia nigra (SN) region of the brain. The cypermethrin model of PD is characterized by mitochondrial dysfunction, autophagy impairment, oxidative stress, etc. However, the effect of cypermethrin on metal homeostasis is not yet explored. The study was designed to delineate the role of metals and their transporter proteins in cypermethrin-induced animal and cellular models of PD. The level of copper, magnesium, iron, and zinc was checked in the nigrostriatal tissue and serum by atomic absorption spectroscopy. Since cypermethrin consistently increased iron content in the nigrostriatal tissue and serum after 12 weeks of exposure, the level of iron transporter proteins, such as divalent metal transporter-1 (DMT-1), ceruloplasmin, transferrin, ferroportin, and hepcidin, and their in silico interaction with cypermethrin were checked. 3,3′-Diaminobenzidine-enhanced Perl’s staining showed an elevated number of iron-positive cells in the SN of cypermethrin-treated rats. Molecular docking studies revealed a strong binding affinity between cypermethrin and iron transporter protein receptors of humans and rats. Furthermore, cypermethrin increased the expression of DMT-1 and hepcidin while reducing the expression of transferrin, ceruloplasmin, and ferroportin in the nigrostriatal tissue and human neuroblastoma cells. These observations suggest that cypermethrin alters the expression of iron transporter proteins leading to iron dyshomeostasis, which could contribute to dopaminergic neurotoxicity. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Facile construction of 4H-chromenes via Michael addition of phenols to benzylidene oxobutanoates and their successful conversion into pyranocoumarins
(Elsevier Ltd, 2018) Priyanka; Rajesh K. Sharma; Ray J. Butcher; Diksha Katiyar
An efficient and simple approach for the synthesis of functionalized 4H-chromenes has been developed via acid catalyzed Michael addition of phenols to benzylidene oxobutanoates. Preliminary mechanistic studies were conducted, suggesting that intermediate chroman derivative is initially formed which on dehydration produces final 4H-chromene. The conversion of 4H-chromenes into linear and angular pyranocoumarins is also described. The structural arrangements between the pyran and coumarin rings have been established by X-ray crystallographic analysis and 2D NMR spectroscopy. © 2018 Elsevier Ltd
In silico designing and interaction of coumarin-amino acid(S) conjugates with integrin like protein of cryptococcus neoformans: Insights on antifungal drug design
(AMG Transcend Association, 2021) Neha Tiwari; Gunjan Uttam; Priyanka; Karuna Singh; Diksha Katiyar
In the present work, a library of 117 coumarin-amino acid(s) conjugates was designed, and molecular docking study was performed to investigate their possible role as fungal integrin like receptor antagonists. The objective of this study is in-silico designing and docking of coumarin-amino acid conjugates against integrin like protein of Cryptococcus neoformans. In the absence of a crystallographic structure of integrin of the fungal pathogen, a homology model of protein OXH63806.1 of Cryptococcus neoformans was developed using the currently available X-ray structure of human integrin as a template. The quality of the 3D model obtained by homology modeling was evaluated by the PROCHECK program. A docking study using coumarin-amino acid(s) conjugates as ligands on the binding site of the modeled receptor was carried out to understand the protein-ligand binding interactions. Some of the compounds have shown very good binding energies ranging from-10.32 to-10.94 Kcal/mol towards the target receptor. These results may be helpful in the designing and development of new antifungal agents as integrin like protein antagonists. © 2020 by the authors.
Isolation and purification of antibacterial compound from streptomyces levis collected from soil sample of north India
(Public Library of Science, 2018) Vineeta Singh; Shafiul Haque; Shruti Khare; Anil Kumar Tiwari; Diksha Katiyar; Bikram Banerjee; Krishna Kumari; C.K.M. Tripathi
During the screening programme for microbial cultures producing antimicrobial agents, an active microbial strain of Streptomyces was isolated from the agricultural soil of Narnaul, Haryana India. Physiological, biochemical characteristics and 16S ribosomal RNA sequence homology studies revealed that it was similar to Streptomyces levis (sequence similarity 100%). The microbial strain was submitted to Genomebio Technologies Pvt. Ltd., Pune, Maharashtra, India under Accession No. EU124569. The isolated strain was found to produce extracellular active compound showing strong antimicrobial activity against Klebsiella pneumoniae MTCC 109, Pseudomonas aeruginosa MTCC 741 and Staphylococcus aureus MTCC 96. The antibacterial compound was successfully isolated and purified. Structure elucidation of antibacterial metabolite with EI-MS/ HRMS showed molecular ion peak at m/z 686 [M+H]+. Whereas, elemental analysis of the said compound showed C = 61.31, H = 8.61, N = 2.04 and O = 28.02, and indicated a molecular formula of C35H59NO12. The presence of ‘chromone’ nucleus in the compound’s chemical structure was confirmed by using 1HNMR studies. The present study reports the purification of potential antibacterial compound from Streptomyces levis isolated from the unexplored soil of north India and warrants for further characterization of this potential compound for optimum utilization for antimicrobial purposes. © 2018 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
l-Proline catalyzed condensation of salicylaldehydes with ethyl nitroacetate: an efficient access to 3-nitrocoumarins
(Springer-Verlag Wien, 2016) Rajesh Kumar Sharma; Priyanka; Diksha Katiyar
Abstract: l-Proline catalyzed condensation of salicylaldehydes and ethyl nitroacetate afforded 3-nitrocoumarins in good to high yields under mild conditions. This organocatalyzed process offers a much improved yield of 3-nitrocoumarins and well tolerates both electron-donating and electron-withdrawing substituents on the phenyl ring. Graphical abstract: [Figure not available: see fulltext.] © 2016, Springer-Verlag Wien.
One-pot amberlite IR-120 catalysed synthesis of glycosyl dihydropyridones
(2007) Vinod K. Tiwari; Neetu Tewari; Diksha Katiyar; Rama P. Tripathi
The one-pot reaction of β-glycosyl amino acids with β-ketoesters in the presence of Amberlite IR-120 resin and 4∈Å molecular sieve in refluxing toluene resulted in the respective dihydropyridones in fair to good yields. © 2007 Springer-Verlag.
Paradendryphiella arenariae (MW504999) as a Novel Fungal Source of Tenuazonic Acid in Tomato (Lycopersicon esculentum)
(Springer, 2025) Ankita Kumari; Karuna Singh; Neha Tiwari; Diksha Katiyar; Satyendra Pratap Singh; Anurag Mishra
Tenuazonic acid (TeA) is a mycotoxin usually produced by Alternaria species. Its toxicological potency is considered to be the highest among all Alternaria-mycotoxins. The present study for the first time reports Paradendryphiella arenariae isolated from tomato (Lycopersicon esculentum) as a source of TeA mycotoxin, thus adding a new genus to the array of TeA-producing fungi. The study involves optimizing culture conditions for maximum TeA production, and employing analytical techniques to characterize the compound. Thin-layer chromatography and high-pressure liquid chromatography (HPLC) were employed for the isolation and characterization of the mycotoxin produced by P. arenariae. Structural elucidation was achieved using Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. Quantitative determination of TeA was conducted using HPLC with a standard TeA reference. The presence of TeA was further confirmed through electronspray ionization-mass spectrometry and high-resolution liquid chromatography-mass spectrometry. In cytotoxicity assays, the isolated TeA exhibited significant toxicity to murine splenocytes, with an IC50 of 25 µg/mL. This study highlights the need for vigilance regarding TeA contamination in food products. The identification of P. arenariae as a new source of TeA underscores the importance of expanding monitoring efforts to include diverse fungal species. Ensuring food safety through stringent regulations and routine testing is essential to mitigate health risks associated with TeA exposure. © Association of Microbiologists of India 2025.
Recent advances in the development of coumarin derivatives as antifungal agents
(Springer Singapore, 2019) Rajesh Kumar Sharma; Diksha Katiyar
Coumarin is a privileged scaffold found in numerous pharmaceutically important natural products and synthetic molecules. The compounds bearing coumarin moiety exhibit broad spectrum of biological properties such as antibacterial, antiviral, anticancerous, anti-inflammatory, antihyperglycemic, and antipyretic activities. Coumarins are also well-known for their antifungal properties. In recent past, several literature reports have been published which highlight the importance of coumarin motif in the area of antifungal drug development. The present contribution provides an overview of synthetic and natural coumarins which have demonstrated potent antifungal activity, reported during 1992-2017. Structure Activity Relationship (SAR) may help medicinal chemists in the rational design and synthesis of new compounds based on coumarin scaffold for the treatment of fungal infections. © Springer Nature Singapore Pte Ltd. 2019.
Recent Advances in Transition-Metal-Catalyzed Synthesis of Coumarins
(Georg Thieme Verlag, 2016) Rajesh Kumar Sharma; Diksha Katiyar
Coumarin is a privileged scaffold found in a large number of biologically active natural products, pharmaceuticals and agrochemicals, and functionalized coumarins are also widely employed as materials. For this reason, considerable interest has been focused on the development of new protocols to access this heterocyclic moiety in the past few decades. Among the numerous methods developed so far, transition-metal-catalyzed reactions are the most attractive methodologies for the synthesis of coumarins under rather mild reaction conditions. This review provides an overview of the recent developments in this field. 1 Introduction 2 Palladium Catalysis 3 Platinum Catalysis 4 Cobalt Catalysis 5 Copper Catalysis 6 Gold Catalysis 7 Iron Catalysis 8 Nickel Catalysis 9 Rhodium Catalysis 10 Ruthenium Catalysis 11 Zinc Catalysis 12 Conclusion. ©.
Resolution, absolute configuration and antifilarial activity of coumarinyl amino alcohols
(Elsevier Ltd, 2017) Priyanka; Sweta Misra; Shailja Misra-Bhattacharya; Ray J. Butcher; Diksha Katiyar
The resolution of racemic coumarinyl amino alcohols 5–10 was achieved by using the inexpensive and readily accessible chiral resolving agent N-carbethoxy-L-proline (S)-11. Direct esterification of rac-5–10 with (S)-11 furnished diastereomeric esters, which were easily separated by column chromatography. The obtained diastereomers yielded the desired enantiopure coumarinyl amino alcohols (S)-(+)-5–10 and (R)-(−)-5–10 in good yields with high enantiomeric excess on saponification. The absolute configurations were determined by X-ray crystal analysis and/or by comparison of the specific rotations. Furthermore, in in vitro antifilarial motility inhibition assays, enantiopure coumarins (S)-(+)-9, (R)-(−)-9 and (S)-(+)-10, (R)-(−)-10 were found to be less efficient in affecting the viability of macrofilariae of Brugia malayi than their racemic forms 9 and 10, respectively, indicating the synergistic effect of the enantiomers in evoking antifilarial action. © 2017 Elsevier Ltd
Synthesis and Antifungal Activity of Some Novel Coumarin-Amino Acid Conjugates
(John Wiley and Sons Inc, 2022) Neha Tiwari; Ankita Kumari; Gunjan Uttam; Vineeta Singh; Karuna Singh; Diksha Katiyar
A series of novel coumarin-amino acid conjugates was synthesized and structural characterization was done by various spectroscopic methods. All the conjugates were screened for their antifungal activity against five fungal strains namely T. rubrum, A. niger, A. fumigatus, A. flavus and C. albicans by two-fold serial microdilution method. Some of them showed significant activity with MIC values in the range of 6.25–25 μg/mL. Notably, compound 5 e showed potential antifungal effect against three tested strains with MIC's in the range of 6.25–12.5 μg/mL. The molecular docking studies showed that some conjugates possessed good binding affinity with the modelled receptor of integrin-like protein of Cryptococcus neoformans var. grubii. Compounds 5 d and 5 e also exhibited good binding efficiency with the Candida spp. cell wall associated proteins in in vitro binding assay. Additionally, in silico physicochemical parameters such as lipophilicity and pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) of the synthesized compounds were also evaluated. © 2022 Wiley-VCH GmbH.
Synthesis and biological evaluation of 4-oxycoumarin derivatives as a new class of antifilarial agents
(Elsevier Masson SAS, 2015) Sweta Misra; Lav Kumar Singh; Priyanka; Jyoti Gupta; Shailja Misra-Bhattacharya; Diksha Katiyar
Abstract A series of 4-oxycoumarin derivatives was synthesized, characterized and evaluated in vitro and in vivo for antifilarial activity against the human lymphatic filarial parasite, Brugia malayi. A majority of the compounds studied showed potent in vitro activity with low IC50 values in the micro molar (μM) range (0.014-1.73 and 0.0056-0.43) against adult worms and microfilariae, respectively. Compounds 8 and 9 were identified to be the most promising antifilarial candidate molecules exhibiting activity in the nanomolar (nM) range. The IC50 values for compound 8 were 14 nM and 5.6 nM while for compound 9 were 94 nM and 13 nM, respectively, for adult worm and microfilaria. These two compounds also displayed promising adulticidal activity (74.9 ± 4.8% and 69.4 ± 2.8%, respectively) in the primary rodent (jird) screen. This study also serves as a starting point for investigating structure-activity relationship with different amino substituents. © 2015 Published by Elsevier Masson SAS.
Synthesis, antimicrobial and chitinase inhibitory activities of 3-amidocoumarins
(Academic Press Inc., 2020) Rajesh Kumar Sharma; Vineeta Singh; Neha Tiwari; R.J. Butcher; Diksha Katiyar
A series of 3-amidocoumarins has been synthesized and tested in vitro for their anitimicrobial and chitinase inhibitory activities. Among these, compounds 5k, 5l, 8b–8d, 8f and 8g exhibited good antibacterial activity with MIC values in the range of 6.25–25 µg/mL against some of the tested strains while compounds 5l, 8b, 8c and 8f showed good activity against at least one or two fungal strains. Some of the assayed compounds 5d, 5k, 5l, 8b and 8c displayed significant chitinase inhibitory activity with IC50 values in the range of 3.74–5.6 µM. Among them, 5l proved to be potent chitinase inhibitor with IC50 value of 3.74 µM. To better understand the enzyme-inhibitor interactions molecular docking study of all the synthesized compounds was carried out on Aspergillus fumigatus chitinase 1W9U. The compound 5l showed high binding affinity with the receptor with binding energy value of −8.44 Kcal/mol. This study also provides structure activity relationship (SAR) of synthesized compounds. © 2020 Elsevier Inc.
Synthesis, antimicrobial, cytotoxic and E. coli DNA gyrase inhibitory activities of coumarinyl amino alcohols
(Academic Press Inc., 2017) Priyanka; Vineeta Singh; Ekta; Diksha Katiyar
Here we report the in vitro antimicrobial activity (minimum inhibitory concentration) of fourteen coumarinyl amino alcohols 2–16 against eight bacterial strains and two fungi. Among these compounds 4, 8, 12, 15 and 16 showed moderate to good microbial inhibition with MIC values varied from 6.25 to 25 μg/mL. The most promising compounds were also evaluated for their in vitro cytotoxic and E. coli DNA gyrase inhibitory activities along with the two 7-oxy-4-methyl coumarinyl amino alcohol derivatives 17 and 18, which were found to be the most potent in in vitro antimicrobial screening in our previous study. All the active compounds, including 17 and 18, were also docked into the E. coli DNA gyrase ATP binding site (PDB ID: 1KZN) to investigate their binding interactions. Of these compound 17 has shown maximum binding energy value of −6.13 kcal/mol. © 2017 Elsevier Inc.
Synthesis, In Vitro and In Vivo Antifungal Activities of Novel Coumarin–Tryptophan Conjugates
(Pleiades Publishing, 2025) Neha Tiwari; Ankita Kumari; Saurabh Sharma; Vaishali Raghuvanshi; Gunjan Uttam; Vineeta K. Singh; Karuna Singh; Diksha Katiyar
Abstract: Objective: Persistent fungal infections, especially those caused by Candida spp., pose a serious health risk to humans. Treatment of these infections is highly challenging due to the spread of resistance to first-line antifungal drugs. Therefore, the identification and development of novel antifungal agents are in great demand. In this study, a series of coumarin–tryptophan conjugates were synthesized and their antifungal activities evaluated. Methods:In vitro antifungal activities of compounds (IVa–IVe) were determined by the minimum inhibitory concentration (MIC) method. The in vivo activity of the most active compound, (IVe), was assessed using a murine model of dermal candidiasis. Docking studies were performed using the AutoDock 4.0 software package. Results and Discussion: Several compounds exhibited broad-spectrum activity against the tested strains, with favorable MIC values in the range of 6.25–25 µg/mL. Compound (IVe) showed significant antifungal activity with an MIC of 6.25 µg/mL against A. flavus and C. albicans. In the murine dermal candidiasis model, (IVe) reduced the fungal burden in nearly all vital organs of the experimental animals and demonstrated therapeutic healing effects on ulcers induced by C. albicans infection. Molecular docking results indicated that these compounds have potential as antifungal agents. Evaluation of drug-like properties of compounds (IVa–IVe) using the SwissADME web tool revealed that these molecules possess favorable druggability profiles. Conclusions: Compound (IVe), having shown excellent antifungal activity, can be considered a promising antifungal agent for further investigation. © Pleiades Publishing, Ltd. 2025.