Novel hepatotrophic prodrugs of the antiviral nucleoside 9-(2-phosphonylmethoxyethyl)adenine with improved pharmacokinetics and antiviral activity.

The device of new hepatotrophic prodrugs of the antiviral nucleoside 9-(2-phosphonylmethoxyethyl)adenine (PMEA) with specificity for the asialoglycoprotein receptor on parenchymal liver cells is described. PMEA was conjugated to bi- and trivalent cluster glycosides (K(GN)(2) and K(2)(GN)(3), respectively) with nanomolar affinity for the asialoglycoprotein receptor. The liver uptake of the PMEA prodrugs was more than 10-fold higher than that of the parent drug (52+/-6% and 62+/-3% vs. 4.8+/-0.7% of the injected dose for PMEA) and could be attributed for 90% to parenchymal cells. Accumulation of the PMEA prodrugs in extrahepatic tissue (e.g., kidney, skin) was substantially reduced. The ratio of parenchymal liver cell-to-kidney uptake-a measure of the prodrugs therapeutic window-was increased from 0.058 +/- 0.01 for PMEA to 1.86 +/- 0.57 for K(GN)(2)-PMEA and even 2.69 +/- 0.24 for K(2)(GN)(3)-PMEA. Apparently both glycosides have a similar capacity to redirect (antiviral) drugs to the liver. After cellular uptake, both PMEA prodrugs were converted into the parent drug, PMEA, during acidification of the lysosomal milieu (t(1/2) approximately 100 min), and the released PMEA was rapidly translocated into the cytosol. The antiviral activity of the prodrugs in vitro was dramatically enhanced as compared to the parent drug (5- and 52-fold for K(GN)(2)-PMEA and K(2)(GN)(3)-PMEA, respectively). Given the 15-fold enhanced liver uptake of the prodrugs, we anticipate that the potency in vivo will be similarly increased. We conclude that PMEA prodrugs have been developed with greatly improved pharmacokinetics and therapeutic activity against viral infections that implicate the liver parenchyma (e.g., HBV). In addition, the significance of the above prodrug concept also extends to drugs that intervene in other liver disorders such as cholestasis and dyslipidemia.     

The synthesis of arginine derivatives of chromone and azauracil

The coupling of N-succinimide esters of 3-[7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)-6-ethyl-4-oxo-4H-chromen-2-yl]propanoic acid and 5-carboxymethyl-6-azauracil with free arginine yielded the corresponding arginine derivatives, which were purified by crystallization. The structures of the compounds were confirmed by ¹H NMR spectroscopy     

Syntheses and biological activities of pyranyl-substituted cinnamates

Twenty-two kinds of pyranyl-substituted cinnamates were synthesized by the reaction of 4-hydroxy-6-(2-phenylethyl)-2H-pyran-2-one or 4-hydroxy-6-methyl-2H-pyran-2-one (HMP) with a variety of substituted cinnamic acids, and their antifungal and plant growth inhibitory activities were investigated. Among the compounds prepared, 6-methyl-2-oxo-2H-pyran-4-yl 3-(4-isopropylphenyl)propenoate (H5) showed the strongest antifungal activity against Rhizoctonia solani and Sclerotium dellfinii, and 6-methyl-2-oxo-2H-pyran-4-yl 3-(2-methylphenyl)propenoate (H2) had the highest plant growth inhibitory activity toward Brassica rapa.     

The synthesis of arginine derivatives of chromone and azauracil

The coupling of N-succinimide esters of 3-[7-hydroxy-3-(4-methyl-1,3-thiazol-2-yl)-6-ethyl-4-oxo-4H-chromen-2-yl]propanoic acid and 5-carboxymethyl-6-azauracil with free arginine yielded the corresponding arginine derivatives, which were purified by crystallization. The structures of the compounds were confirmed by 1H NMR spectroscopy. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.     

Antiviral potential of a new generation of acyclic nucleoside phosphonates, the 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines

Three acyclic nucleoside phosphonates (ANPs) have been formally approved for clinical use in the treatment of 1) cytomegalovirus retinitis in AIDS patients (cidofovir, by the intravenous route), 2) chronic hepatitis B virus (HBV) infections (adefovir dipivoxil, by the oral route), and 3) human immunodeficiency virus (HIV) infections (tenofovir disoproxil fumarate, by the oral route). The activity spectrum of cidofovir {(S)- 1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine [(S)-HPMPC)]}, like that of (S)-HPMPA [(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine) and (S)-HPMPDAP [(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2, 6-diaminopurine), encompasses a broad spectrum of DNA viruses, including polyoma-, papilloma-, adeno-, herpes-, and poxviruses. Adefovir {9-[2-(phosphonomethoxy)ethyl]adenine (PMEA)} and tenofovir [(R)-9-[2-(phosphonomethoxy) propyl]adenine [(R)-PMPA)]} are particularly active against retroviruses (ie., HIV) and hepadnaviruses (ie., HBV); additionally, PMEA also shows activity against herpes- and poxviruses. We have recently identified a new class of ANPs, namely 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines, named, in analogy with their alkylpurine counterparts, HPMPO-DAPy, PMEO-DAPy, and (R)-PMPO-DAPy. These compounds exhibit an antiviral activity spectrum and potency that is similar to that of (S)-HPMPDAP, PMEA, and (R)-PMPA, respectively. Thus, PMEO-DAPy and (R)-PMPO-DAPy, akin to PMEA and (R)-PMPA, proved particularly active against HIV- 1, HIV-2, and the murine retrovirus Moloney sarcoma virus (MSV). PMEO-DAPy and (R)-PMPO-DAPy also showed potent activity against both wild-type and lamivudine-resistant strains of HBV. HPMPO-DAPy was found to inhibit different poxviruses (ie., vaccinia, cowpox, and orf) at a similar potency as cidofovir. HPMPO-DAPy also proved active against adenoviruses. In vivo, HPMPO-DAPy proved equipotent to cidofovir in suppressing vaccinia virus infection (tail lesion formation) in immunocompetent mice and promoting healing of disseminated vaccinia lesions in athymic-nude mice. The 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines offer substantial potential for the treatment of a broad range of retro-, hepadna-, herpes-, adeno-, and poxvirus infections.     

Identification of antibacterial and antiviral activities of novel fused 1,2,4-triazine esters

The in vitro biological activities of novel derivatives of methyl and ethyl 2-(4-oxo-8-aryl-2H-3,4,6,7-tetrahydroimidazo[2,1-c][1,2,4]triazin-3-yl)acetates (3a, 3d-j) have been evaluated and are reported. The final heterobicycles (3a-j) were obtained from monocyclic 1-aryl-2-hydrazonoimidazolidines (2a-f) by addition and cyclization reaction with fumaric acid esters. In particular, compounds 3d and 3e were found to exhibit comparable antibacterial potencies in vitro as that of ampicillin. Heterobicycles of the 3e, 3g and 3j type were screened for their antiviral activities against the selected viruses' DNA (human adenovirus type 5-Ad-5) and RNA (human enterovirus-Echo-9). Simultaneously, their cytotoxicities towards HEK-293 and GMK cells were established. In particular, heterobicycle 3j, completely non-toxic for GMK cells, was found to exhibit virucidal properties against Echo-9 virus justifying its further investigation as the potential antiviral agent.     

Novel ofloxacin derivatives: synthesis, antimycobacterial and toxicological evaluation

Thirty novel 9-fluoro-2,3-dihydro-8,10-(mono/di-sub)-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acids were synthesized from 2,3,4,5-tetrafluoro benzoic acid and evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC(2)) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from mycobacteria. Among the synthesized compounds, 10-[2-carboxy-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be the most active compound in vitro with MIC99 of 0.19 microM and 0.09 microM against MTB and MTR-TB, respectively. In the in vivo animal model also the same compound decreased the bacterial load in lung and spleen tissues with 1.91 and 2.91--log10 protections, respectively, at the dose of 50mg/kg body weight. Compound 10-[(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be the most active in the inhibition of the supercoiling activity of DNA gyrase with an IC(50) of 10.0 microg/mL. The results demonstrate the potential and importance of developing new oxazino quinolone derivatives against mycobacterial infections.     

Synthesis,biological activity and multiscale molecular modeling studies of bis-coumarins as selective carbonic anhydrase IX and XII inhibitors with effective cytotoxicity against hepatocellular carcinoma

A series of novel bis-coumarin derivatives containing triazole moiety as a linker between the alkyl chains was synthesized and their inhibitory activity against the human carbonic anhydrase (hCA) isoforms I, II, IX and XII were evaluated. In addition, cytotoxic effects of the synthesized compounds on renal adenocarcinoma (769P), hepatocellular carcinoma (HepG2) and breast adeno carcinoma (MDA-MB-231) cell lines were examined. While the hCA I and II isoforms were inhibited in the micromolar range, the tumor-associated isoform hCA IX and XII were inhibited in the high nanomolar range. 4-methyl-7-((1-(12-((2-oxo-2H-chromen-7-yl)oxy)dodecyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (5p) showed the strongest inhibitory activity against hCA IX with the K_i of 144.6 nM and 4-methyl-7-((1-(10-((2-oxo-2H-chromen-7-yl)oxy)decyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (5n) exhibited the highest hCA XII inhibition with the K_i of 71.5 nM. In order to better understand the inhibitory profiles of studied molecules, multiscale molecular modelling approaches were applied. Low energy docking poses of studied molecules at the binding sites of targets have been predicted. In addition, electrostatic potential surfaces (ESP) for binding sites were also generated to understand interactions between proteins and active ligands.     

ANTIVIRAL POTENTIAL OF A NEW GENERATION OF ACYCLIC NUCLEOSIDE PHOSPHONATES,THE 6-[2-(PHOSPHONOMETHOXY)ALKOXY]-2,4-DIAMINOPYRIMIDINES

Three acyclic nucleoside phosphonates (ANPs) have been formally approved for clinical use in the treatment of 1) cytomegalovirus retinitis in AIDS patients (cidofovir, by the intravenous route), 2) chronic hepatitis B virus (HBV) infections (adefovir dipivoxil, by the oral route), and 3) human immunodeficiency virus (HIV) infections (tenofovir disoproxil fumarate, by the oral route). The activity spectrum of cidofovir {(S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine [(S)-HPMPC)]}, like that of (S)-HPMPA {(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine} and (S)-HPMPDAP {(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine}, encompasses a broad spectrum of DNA viruses, including polyoma-, papilloma-, adeno-, herpes-, and poxviruses. Adefovir {9-[2-(phosphonomethoxy)ethyl]adenine (PMEA)} and tenofovir {(R)-9-[2-(phosphonomethoxy) propyl]adenine [(R)-PMPA)]} are particularly active against retroviruses (i.e., HIV) and hepadnaviruses (i.e., HBV); additionally, PMEA also shows activity against herpes- and poxviruses. We have recently identified a new class of ANPs, namely 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines, named, in analogy with their alkylpurine counterparts, HPMPO-DAPy, PMEO-DAPy, and (R)-PMPO-DAPy. These compounds exhibit an antiviral activity spectrum and potency that is similar to that of (S)-HPMPDAP, PMEA, and (R)-PMPA, respectively. Thus, PMEO-DAPy and (R)-PMPO-DAPy, akin to PMEA and (R)-PMPA, proved particularly active against HIV-1, HIV-2, and the murine retrovirus Moloney sarcoma virus (MSV). PMEO-DAPy and (R)-PMPO-DAPy also showed potent activity against both wild-type and lamivudine-resistant strains of HBV. HPMPO-DAPy was found to inhibit different poxviruses (i.e., vaccinia, cowpox, and orf) at a similar potency as cidofovir. HPMPO-DAPy also proved active against adenoviruses. In vivo, HPMPO-DAPy proved equipotent to cidofovir in suppressing vaccinia virus infection (tail lesion formation) in immunocompetent mice and promoting healing of disseminated vaccinia lesions in athymic-nude mice. The 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines offer substantial potential for the treatment of a broad range of retro-, hepadna-, herpes-, adeno-, and poxvirus infections.     

Novel angular furoquinolinones bearing flexible chain as antitumor agent: design, synthesis, cytotoxic evaluation, and DNA-binding studies

A series of novel N-substituted angular furoquinolinone derivatives were synthesized and evaluated for their antitumor activities against QGY, K562, HeLa, P388, and A549 cell lines in vitro. The derivatives bearing basic amino side chain showed an improved antitumor activity. Compound 5h N-(2-dimethylamino-ethyl)-2-(4,8,9-trimethyl-2-oxo-2H-furo[2,3-h]quinolin-1-yl)-acetamide exhibited the highest activities against P388 and A549 cell lines, which are evidenced by the IC(50) values that are four to five fold lower than that for unsubstituted parent compound. DNA-binding experiments suggested that these derivatives bind to DNA through intercalation.     

In vivo Antiretroviral Efficacy of Oral bis(POM)-PMEA,the bis(Pivaloyloxymethyl)prodrug of 9-(2-Phosphonylmethoxyethyl) adenine (PMEA)

Abstract

The bis-pivaloyloxymethyl(POM)- and diphenyl-ester prodrugs of the broad spectrum antiviral agent 9-(2-phosphonylmethoxyethyl)adenine (PMEA) have been evaluated in vivo for antiviral efficacy upon oral administration in severe combined immune deficiency (SCID) mice infected with Moloney murine sarcoma virus (MSV). Oral bis (POM)-PMEA proved highly efficient in delaying MSV-induced tumor formation and associated death, its effect being equal to that of subcutaneous PMEA at an equimolar dose. Compared to bis(POM)-PMEA, oral diphenyl-PMEA had lower antiviral efficacy, whereas PMEA as such was poorly effective when administered orally. Our studies indicate that bis(POM)-PMEA must have a favorable oral bioavailability and justify its clinical investigation as an oral prodrug of PMEA in the treatment of HIV infections.     

Synthesis of stavudine amino acid ester prodrugs with broad-spectrum chemotherapeutic properties for the effective treatment of HIV/AIDS

A series of prodrugs of stavudine were synthesized in an effort to enhance spectrum of chemotherapeutic properties for the effective treatment of HIV/AIDS. The 5'-OH function of stavudine was esterified with ciprofloxacin, norfloxacin, isoniazide, pyrazinamide, piperazine and dimethylamine acetic acid. The anti-HIV-1 activity of the esters was determined in CEM cell line and stavudine ester bearing piperazine acetic acid was found to be the most potent compound with a selective index of >15,723. Stavudine prodrug bearing ciprofloxacin and norfloxacin acetic acid showed 100% inhibition against Mycobacterium tuberculosis H(37)Rv at 6.25 microg/mL. The prodrugs also exhibited antibacterial activity against 24 pathogenic bacteria. In vitro hydrolysis of the various esters in human plasma indicated that these agents were relatively stable toward plasma esterases with t(1/2) ranging from 20-240 min.     

Synthesis and antiviral evaluation of 2-amino-6-carbamoylpurine dioxolane nucleoside derivatives and their phosphoramidates prodrugs

The synthesis of 9-(β-d-1,3-dioxolan-4-yl)2,6-diaminopurine nucleoside phosphoramidate prodrugs as well as various 2-amino-6-carbamoylpurine dioxolane derivatives and their phosphoramidates prodrugs is reported. Their ability to block HIV and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte, CEM and Vero cells was also assessed.     

Design, synthesis, and evaluation of novel 4-thiazolylimidazoles as inhibitors of transforming growth factor-β type I receptor kinase

A novel series of 4-thiazolylimidazoles was synthesized as transforming growth factor-β (TGF-β) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-β-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. N-{[5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-2-yl]methyl}butanamide 20, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC(50)=8.2nM) as well as inhibitory activity against TGF-β-induced Smad2/3 phosphorylation at a cellular level (IC(50)=32nM).     

By-products in the analysis of beta-muricholic acid in biological samples as methyl ester triacetate

By-products were formed on analysis of beta-muricholic acid (3 alpha, 6 beta, 7 beta-trihydroxy-5 beta-cholan-24-oic acid) in biological samples by a method involving acid-catalyzed solvolysis of sulfate esters in acetone-methanol, followed by perchloric acid-catalyzed acetylation with acetic anhydride-acetic acid. These products have been identified by mass spectrometry and nuclear magnetic resonance as methyl 3-0,6-0-diacetyl-7-0-(1-methyl-3-oxo-1-butenyl)- and methyl 3-0,7-0-diacetyl-6-0-(1-methyl-3-oxo-1-butenyl)-beta-muricholate, methyl 3-0, 6-0-diacetyl- and methyl 3-0, 7-0-diacetyl-beta-muricholate, and a methyl diacetoxy-cholen-24-oate.     

Synthesis of some new hybride molecules containing several azole moieties and investigation of their biological activities

1,2,4-Triazole-3-one prepared from tryptamine was converted to the corresponding carbothioamides by several steps. Their treatment with ethyl bromoacetate or 4-chlorophenacyl bromide produced the corresponding 5-oxo-1,3-thiazolidine or 3-(4-chlorophenyl)-1,3-thiazole derivatives. Acetohydrazide derivative that was obtained starting from tryptamine, was converted to the corresponding Schiff basis and sulfonamide by the treatment with suitable aldehydes and benzensulphonyl chloride, respectively. 2-[(4-Amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)methyl]-4-[2-(1H-indole-3-yl)ethyl]-5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-one was synthesized starting from hydrazide via the formation of the corresponding 1,3,4-oxadiazole compound, while the other bitriazole compounds were obtained by intramolecular cyclisation of carbothioamides in basic media. The treatment of 1,2,4-triazole or 1,3,4-oxadiazole compound with several amines generated the corresponding Mannich bases. Ethyl (2-amino-1,3-thiazole-4-yl)acetate was converted to the corresponding 1,3,4-oxadiazole derivative, arylidenehydrazides, 1,2,4-triazole-3-one and 5-oxo-1,3-oxazolidine derivatives by several steps. The structural assignments of new compounds were based on their elemental analysis and spectral (FT IR, ¹H NMR, ¹³C NMR and LC-MS) data. The antimicrobial, antilipase and antiurease activity studies revealed that some of the synthesized compounds showed antimicrobial, antilipase and/or antiurease activity.     

Synthesis and in vitro anti-HIV activities of didanosine prodrugs

A series of prodrugs of didanosine were synthesized in an effort to enhance the anti-HIV activity. The 5'-OH function of didanosine was esterified with different aryl piperazine acetic acid derivatives and evaluated for anti-HIV-1 activity in MT-4 cell line using the MTT assay method. Among the synthesized compounds, (tetrahydro-5-(1,6-dihydro-6-oxopurin-9-yl)furan-2-yl)methyl 2-(4-(4-chlorophenyl)piperazin-1-yl)acetate (4b) was found to be the most potent compound with EC50 of 0.64 microM and was not toxic to the MT-4 cells up to 1000 microM with a selectivity index of > 1562. Compound 4b was found to be seven times more potent than the parent drug didanosine (EC50 of 4.8 microM) in vitro. In vitro hydrolysis of the various esters in human plasma indicated that these agents were relatively stable toward plasma esterases with t1/2 ranging from 20-60 min.     

Synthesis and biological evaluation of some novel triazol-3-ones as antimicrobial agents

A new series of triazol-3-one derivatives bearing 4-methyl-4H-thieno[3',2': 5,6]thiopyrano[4,3-d][1,3]thiazolyl or 4-(thiophene-3-yl) thiazolyl moiety at 4-position and alkyl substitution at 2-position are synthesized. All the synthesized compounds are characterized by elemental analysis, IR, (1)H NMR, (13)C NMR, and mass spectral data. The newly synthesized compounds are screened for antifungal and antibacterial activities.     

Evidence that heme d1 is a 1,3-porphyrindione

Heme d1 is the noncovalently associated heme prosthetic group of the bacterial nitrite reductase known as cytochrome cd1. Additional evidence has been obtained in support of a dioxoisobacteriochlorin, or 1,3-porphyrindione, skeleton for this heme. The new data include the natural abundance 13C NMR spectrum of the free base methyl ester derivative of d1, mass spectrometric determinations of the molecular mass of the free base methyl ester and the Cu and the Zn chelates, visible and 1H NMR spectral comparisons between d1 and synthetic porphyrindione model compounds, and the isolation and characterization of several byproducts formed during the purification of the free base methyl ester of d1. The accumulated evidence strongly supports the following structure for the skeleton of d1: 1-oxo-2-methyl-2'-acetyl-3-oxo-4-methyl-4'-acetyl-5-methyl-6-acrylyl+ ++-7- propionyl-8-methylporphyrin.     

Anti-pinworm activity of novel coumarin-based trisubstituted methanes in Syphacia obvelata-infected mice

The control of pinworms mainly relies on use of anthelmintic drugs. At present, there exists only few medications against pinworms, and their repeated use pose a serious risk of resistance development. Therefore, new anti-pinworm drugs are required to overcome the risk of resistance. This study reports the anti-pinworm activity of three novel coumarin-based trisubstituted methanes (TRSMs), i.e., 6-Amino-5-((4-hydroxy-2-oxo-2H-chromen-3-yl)(4-fluoro-phenyl)methyl)-1,3-dimethyl-pyrimidine-2,4(1H,3H)-dione (1), 6-Amino-5-((4-hydroxy-2-oxo-2H-chromen-3-yl)(4-chlor-ophenyl)methyl)-1,3-dimethyl-pyrimidine-2,4(1H,3H)-dione (2) and 6-Amino-5-((4-hydroxy-2-oxo-2H-chromen-3-yl)(4-bromophenyl)methyl)-1,3-dimethyl-pyrimidine-2,4(1H,3H)-dione (3) in Syphacia obvelata-infected mice. The oral acute toxicity of compounds was examined using the OECD guidelines. The findings of this study reveal that TRSM analogues 1 and 2, at a single 80 mg/kg dose given for 5 days, can reduce about 90% of pinworm worm burden in mice, compared to 98% worm reduction shown by 20 mg/kg dose of albendazole, the reference drug, on the 12 day of infection. In particular, the fluoro-and bromo-substituents in the phenyl ring of synthesized derivatives greatly influence the efficacy of candidates. The oral acute toxicity of TRSMs was observed to be greater than 2000 mg/kg body weight for mice. Taken together, our study suggests that studied novel coumarin-based trisubstituted methanes could serve as suitable candidates for the development of new anti-pinworm drugs.