BACKGROUND: Near-infrared spectroscopy has emerged as a revolutionary tool with transformative potential in the biomedical and pharmaceutical realms. AREA COVERED: This article explores the latest trends and advancements in near-infrared spectroscopy applications within these fields. The work begins with current trends and the development of novel miniaturized spectrometers and continues with the applications of near-infrared spectroscopy with other analytical techniques. Highlighted topics encompass the biomedical utilization of near-infrared spectroscopy, ranging from cancer diagnosis to detection of diseases and wounds. Special emphasis is placed on the role of near-infrared spectroscopy in ensuring medicinal quality and combating counterfeit medications, with insights into its advantages for low-cost systems in developing countries. Finally, the article explores near-infrared spectroscopy's role in analyzing natural medicines and presenting a holistic perspective on its diverse applications. EXPERT OPINION: This work demonstrates how the utilization of near-infrared spectroscopy is transforming both biomedical and pharmaceutical sciences landscapes, paving the way for improved patient safety, therapy effectiveness, and global healthcare initiatives.
- Klíčová slova
- Counterfeit identification, Disease detection, Drug analysis, Miniaturized spectrometers, Near-infrared spectroscopy, Non-destructive analysis,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND AND PURPOSE: New compounds and innovative therapeutic approaches are trying to prevent antimicrobial resistance, which has become a global health challenge. EXPERIMENTAL APPROACH: This study includes a series of twelve mono-, di- and trichlorinated 1-hydroxynaphthalene-2-carboxanilides designed as multitarget agents. All compounds were evaluated for their antistaphylococcal activity. Furthermore, MTT assay and chemoproteomic analysis of selected compounds were performed. Cytotoxicity in human cells was also tested. KEY RESULTS: N-(3,5-Dichlorophenyl)-1-hydroxynaphthalene-2-carboxamide (10) demonstrated activity comparable to or higher than clinically used drugs, with minimum inhibitory concentrations (MICs) of 0.37 μM. The compound was equally effective against clinical isolates of methicillin-resistant S. aureus. On the other hand, compound 10 showed 96 % inhibition of S. aureus respiration only at a concentration of 16× MIC. Chemoproteomic analysis revealed that the effect of agent 10 on staphylococci resulted in the downregulation of four proteins. This compound expressed no in vitro cytotoxicity up to a concentration of 30 μM. CONCLUSION: From the set of tested mono-, di- and trisubstituted derivatives, it is evident that the position of chlorine atoms is decisive for significant antistaphylococcal activity. Inhibition of energy metabolism does not appear to be one of the main mechanisms of action of compound 10; on the contrary, the antibacterial effect may likely be contributed by downregulation of proteins (especially ATP-dependent protease ATPase subunit HslU) involved in processes essential for bacterial survival and growth, such as protein, nucleotide/nucleic acid synthesis and efficient protein repair/degradation.
- Klíčová slova
- Lipophilicity, MTT assay, antistaphylococcal activity, chemoproteomic analysis, cytotoxicity,
- Publikační typ
- časopisecké články MeSH
A series of eighteen new 2-trifluoromethylcinnamanilides (1a-r) were synthesized by microwave synthesis and investigated for their antimycobacterial and antimalarial activities, along with the complementary (2E)-3-[3-(trifluoromethyl)phenyl]-N-arylprop-2-enanilides (2a-r) and (2E)-3-[4-(trifluoromethyl)phenyl]-N-arylprop-2-enanilides (3a-r) prepared earlier. All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and a chloroquine-sensitive strain of Plasmodium falciparum 3D7/MRA-102. The most active compounds against M. smegmatis (MIC values in the range of 1.17-11.1 µM, more effective than rifampicin) were anilides substituted by 3,5-CF3 (1q, 2q, 3q), 4-OCF3 (1k), and 4-CF3 (1j, 2j). The most effective agents against P. falciparum (IC50 values in the range of 0.32-4.5 µM, comparable to chloroquine) were anilides substituted by 3,5-CF3 (1q, 2q, 3q), 2-Br-4-OCF3 (1r), 4-CF3 (1j, 3j), 4-F (2d), 4-Cl (2g), 2-Cl (1e, 2e). A preliminary in vitro cytotoxicity screening was assessed using human leukemic cell lines and human dermal fibroblasts, revealing the toxic effect of 3,5-CF3 substituted anilides. On the other hand, the other investigated agents showed insignificant cytotoxic effects. Stability assays using rat liver microsomes demonstrated that compounds 1r (R = 2-Br-4-OCF3) and 1q (R = 3,5-CF3) are neither metabolized nor affect cytochrome P450 metabolizing capacity in vitro. Furthermore, complex in silico studies were performed - a combined approach (docking/MD simulations/QTAIM calculations) helped to define the molecular interactions that were applied during the binding of active agents and the subsequent inhibition of their molecular targets - InhA (activity against M. smegmatis) and arginase (activity against P. falciparum). In conclusion, promising active agents with dual antimycobacterial and antimalarial effects were identified.
- Klíčová slova
- Cinnamanilides, Cytotoxicity, Lipophilicity, M. smegmatis, Molecular modeling, P. falciparum, QTAIM calculations,
- MeSH
- anilidy farmakologie chemie chemická syntéza MeSH
- antibakteriální látky farmakologie chemie chemická syntéza MeSH
- antimalarika * farmakologie chemie chemická syntéza MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- Mycobacterium smegmatis * účinky léků MeSH
- parazitické testy citlivosti MeSH
- Plasmodium falciparum * účinky léků MeSH
- simulace molekulového dockingu MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- anilidy MeSH
- antibakteriální látky MeSH
- antimalarika * MeSH
One of the definitions of chemical biology is that it is a scientific discipline spanning the fields of chemistry, biology, and physics; it primarily involves the application of chemical techniques, tools, analyses, and often compounds (also known as chemical probes), which are produced through synthetic chemistry, in order to study and manipulate biological systems [...].
A series of nine 2,3-disubstituted-quinazolin-4(3H)-one derived Schiff bases and their three Cu(II) complexes was prepared and tested for their antimicrobial activities against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the substances were tested in vitro against Mycobacterium tuberculosis H37Ra ATCC 25177, M. kansasii DSM 44162 and M. smegmatis ATCC 700084. While anti-enterococcal and antimycobacterial activities were insignificant, 3-[(E)-(2-hydroxy-5-nitrobenzylidene)amino]-2-(2-hydroxy-5-nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one (SB3) and its Cu(II) complex (SB3-Cu) demonstrated bacteriostatic antistaphylococcal activity. In addition, both compounds, as well as the other two prepared complexes, showed antibiofilm activity, which resulted in a reduction of biofilm formation and eradication of mature S. aureus biofilm by 80% even at concentrations lower than the values of their minimum inhibitory concentrations. In addition, the compounds were tested for their cytotoxic effect on the human monocytic leukemia cell line THP-1. The antileukemic efficiency was improved by the preparation of Cu(II) complexes from the corresponding non-chelated Schiff base ligands.
- Klíčová slova
- Antibacterial activity, Antibiofilm effect, Cu(II) complexes, Cytotoxicity, Quinazolinones, Schiff bases,
- Publikační typ
- časopisecké články MeSH
A series of seventeen 4-chlorocinnamanilides and seventeen 3,4-dichlorocinnamanilides were characterized for their antiplasmodial activity. In vitro screening on a chloroquine-sensitive strain of Plasmodium falciparum 3D7/MRA-102 highlighted that 23 compounds possessed IC50 < 30 µM. Typically, 3,4-dichlorocinnamanilides showed a broader range of activity compared to 4-chlorocinnamanilides. (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-en-amide with IC50 = 1.6 µM was the most effective agent, while the other eight most active derivatives showed IC50 in the range from 1.8 to 4.6 µM. A good correlation between the experimental logk and the estimated clogP was recorded for the whole ensemble of the lipophilicity generators. Moreover, the SAR-mediated similarity assessment of the novel (di)chlorinated N-arylcinnamamides was conducted using the collaborative (hybrid) ligand-based and structure-related protocols. In consequence, an 'averaged' selection-driven interaction pattern was produced based in namely 'pseudo-consensus' 3D pharmacophore mapping. The molecular docking approach was engaged for the most potent antiplasmodial agents in order to gain an insight into the arginase-inhibitor binding mode. The docking study revealed that (di)chlorinated aromatic (C-phenyl) rings are oriented towards the binuclear manganese cluster in the energetically favorable poses of the chloroquine and the most potent arginase inhibitors. Additionally, the water-mediated hydrogen bonds were formed via carbonyl function present in the new N-arylcinnamamides and the fluorine substituent (alone or in trifluoromethyl group) of N-phenyl ring seems to play a key role in forming the halogen bonds.
- Klíčová slova
- CoMSA, arginase inhibition, arylcinnamamides, lipophilicity, molecular docking, similarity-activity landscape index,
- MeSH
- antimalarika * farmakologie MeSH
- arginasa farmakologie MeSH
- chlorochin farmakologie MeSH
- Plasmodium falciparum MeSH
- simulace molekulového dockingu MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antimalarika * MeSH
- arginasa MeSH
- chlorochin MeSH
A series of thirty-two anilides of 3-(trifluoromethyl)cinnamic acid (series 1) and 4-(trifluoromethyl)cinnamic acid (series 2) was prepared by microwave-assisted synthesis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. (2E)-3-[3-(Trifluoromethyl)phenyl]-N-[4-(trifluoromethyl)phenyl]prop-2-enamide (1j), (2E)-N-(3,5-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]prop-2-enamide (1o) and (2E)-N-[3-(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)-phenyl]prop-2-enamide (2i), (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]-prop-2-enamide (2p) showed antistaphylococcal (MICs/MBCs 0.15-5.57 µM) as well as anti-enterococcal (MICs/MBCs 2.34-44.5 µM) activity. The growth of M. marinum was strongly inhibited by compounds 1j and 2p in a MIC range from 0.29 to 2.34 µM, while all the agents of series 1 showed activity against M. smegnatis (MICs ranged from 9.36 to 51.7 µM). The performed docking study demonstrated the ability of the compounds to bind to the active site of the mycobacterial enzyme InhA. The compounds had a significant effect on the inhibition of bacterial respiration, as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity but also bactericidal activity. Preliminary in vitro cytotoxicity screening was assessed using the human monocytic leukemia cell line THP-1 and, except for compound 2p, all effective agents did show insignificant cytotoxic effect. Compound 2p is an interesting anti-invasive agent with dual (cytotoxic and antibacterial) activity, while compounds 1j and 1o are the most interesting purely antibacterial compounds within the prepared molecules.
- Klíčová slova
- Michael acceptors, antimicrobial activity, cinnamamides, cytotoxicity, docking study, lipophilicity, structure–activity relationships,
- MeSH
- antibakteriální látky farmakologie chemie MeSH
- cinnamáty farmakologie chemie MeSH
- lidé MeSH
- methicilin rezistentní Staphylococcus aureus * MeSH
- mikrobiální testy citlivosti MeSH
- stafylokokové infekce * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- cinnamáty MeSH
- cinnamic acid MeSH Prohlížeč
Due to the urgent need of innovation in the antimalarial therapeutic arsenal, a series of thirty-seven ring-substituted N-arylcinnamanilides prepared by microwave-assisted synthesis were subjected to primary screening against the chloroquine-sensitive strain of P. falciparum 3D7/MRA-102. The lipophilicity of all compounds was experimentally determined as the logarithm of the capacity factor k, and these data were subsequently used in the discussion of structure-activity relationships. Among the screened compounds, fourteen derivatives exhibited IC50 from 0.58 to 31 µM, whereas (2E)-N-(4-bromo-2-chlorophenyl)-3-phenylprop-2-enamide (24) was the most effective agent (IC50 = 0.58 µM). In addition, (2E)-N-[2,6-dibromo-4-(trifluoromethyl)- phenyl]-3-phenylprop-2-enamide (36), (2E)-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-phenylprop- 2-enamide (18), (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide (23), and (2E)-3-phenyl-N-(3,4,5-trichlorophenyl)prop-2-enamide (33) demonstrated efficacy in the IC50 range from 2.0 to 4.3 µM, comparable to the clinically used standard chloroquine. The results of a cell viability screening performed using THP1-Blue™ NF-κB cells showed that none of these highly active compounds displayed any significant cytotoxic effect up to 20 μM, which makes them promising Plasmodium selective substances for further investigations.
- Klíčová slova
- Plasmodium, antiplasmodial activity, cinnamanilides, structure-activity relationships,
- MeSH
- antagonisté kyseliny listové * MeSH
- antimalarika * farmakologie MeSH
- chlorochin farmakologie MeSH
- lidé MeSH
- tropická malárie * MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antagonisté kyseliny listové * MeSH
- antimalarika * MeSH
- chlorochin MeSH
A series of eighteen 4-chlorocinnamanilides and eighteen 3,4-dichlorocinnamanilides were designed, prepared and characterized. All compounds were evaluated for their activity against gram-positive bacteria and against two mycobacterial strains. Viability on both cancer and primary mammalian cell lines was also assessed. The lipophilicity of the compounds was experimentally determined and correlated together with other physicochemical properties of the prepared derivatives with biological activity. 3,4-Dichlorocinnamanilides showed a broader spectrum of action and higher antibacterial efficacy than 4-chlorocinnamanilides; however, all compounds were more effective or comparable to clinically used drugs (ampicillin, isoniazid, rifampicin). Of the thirty-six compounds, six derivatives showed submicromolar activity against Staphylococcus aureus and clinical isolates of methicillin-resistant S. aureus (MRSA). (2E)-N-[3,5-bis(trifluoromethyl)phenyl]- 3-(4-chlorophenyl)prop-2-enamide was the most potent in series 1. (2E)-N-[3,5-bis(Trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-enamide, (2E)-3-(3,4-dichlorophenyl)-N-[3-(trifluoromethyl)phenyl]prop-2-enamide, (2E)-3-(3,4-dichloro- phenyl)-N-[4-(trifluoromethyl)phenyl]prop-2-enamide and (2E)-3-(3,4-dichlorophenyl)- N-[4-(trifluoromethoxy)phenyl]prop-2-enamide were the most active in series 2 and in addition to activity against S. aureus and MRSA were highly active against Enterococcus faecalis and vancomycin-resistant E. faecalis isolates and against fast-growing Mycobacterium smegmatis and against slow-growing M. marinum, M. tuberculosis non-hazardous test models. In addition, the last three compounds of the above-mentioned showed insignificant cytotoxicity to primary porcine monocyte-derived macrophages.
- Klíčová slova
- antimicrobial activity, cinnamamides, cytotoxicity, lipophilicity, structure-activity relationships,
- MeSH
- ampicilin farmakologie MeSH
- antibakteriální látky farmakologie MeSH
- methicilin rezistentní Staphylococcus aureus * MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium tuberculosis * MeSH
- prasata MeSH
- savci MeSH
- stafylokokové infekce * MeSH
- Staphylococcus aureus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ampicilin MeSH
- antibakteriální látky MeSH
A set of twenty-four 3-hydroxynaphthalene-2-carboxanilides, disubstituted on the anilide ring by combinations of methoxy/methyl/fluoro/chloro/bromo and ditrifluoromethyl groups at different positions, was prepared. The compounds were tested for their ability to inhibit photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. N-(3,5-Difluorophenyl)-, N-(3,5-dimethylphenyl)-, N-(2,5-difluorophenyl)- and N-(2,5-dimethylphenyl)-3-hydroxynaphthalene-2-carboxamides showed the highest PET-inhibiting activity (IC50 ~ 10 µM) within the series. These compounds were able to inhibit PET in photosystem II. It has been found that PET-inhibiting activity strongly depends on the position of the individual substituents on the anilide ring and on the lipophilicity of the compounds. The electron-withdrawing properties of the substituents contribute towards the PET activity of these compounds.
- Klíčová slova
- PET inhibition, hydroxynaphthalene-carboxamides, spinach chloroplasts, structure-activity relationships,
- MeSH
- chloroplasty účinky léků metabolismus MeSH
- fotosyntéza účinky léků MeSH
- fotosystém II (proteinový komplex) antagonisté a inhibitory metabolismus MeSH
- herbicidy chemie metabolismus MeSH
- naftaleny chemie metabolismus MeSH
- Spinacia oleracea účinky léků metabolismus MeSH
- transport elektronů účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fotosystém II (proteinový komplex) MeSH
- herbicidy MeSH
- naftaleny MeSH
