Synthesis and Bioactivity of Thiazolethioacetamides as Potential Metallo-β-Lactamase Inhibitors

Metallo-β-lactamase (MβLs) mediated antibiotic resistance seriously threatens the treatment of bacterial diseases. Recently, we found that thioacetamides can be a potential MβL inhibitor skeleton. In order to improve the information of the skeleton, twelve new thiazolethioacetamides were designed by modifying the aromatic substituent. Biological activity assays identify the thiazolethioacetamides can inhibit ImiS with IC50 values of 0.17 to 0.70 μM. For two of them, the IC50 values against VIM-2 were 2.2 and 19.2 μM, which is lower than in our previous report. Eight of the thiazolethioacetamides are able to restore antibacterial activity of cefazolin against E.coli-ImiS by 2–4 fold. An analysis of the structure–activity relation and molecule docking show that the style and position of electron withdrawing groups in aromatic substituents play a crucial role in the inhibitory activity of thiazolethioacetamides. These results indicate that thiazolethioacetamides can serve as a potential skeleton of MβL inhibitors.

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Hydrazones of 4-(Trifluoromethyl)benzohydrazide as New Inhibitors of Acetyl- and Butyrylcholinesterase

Molecules ◽

10.3390/molecules26040989 ◽

2021 ◽

Vol 26 (4) ◽

pp. 989

Author(s):

Martin Krátký ◽

Katarína Svrčková ◽

Quynh Anh Vu ◽

Šárka Štěpánková ◽

Jarmila Vinšová

Keyword(s):

Biological Activity ◽

Mixed Type ◽

Cholinesterase Inhibitors ◽

Eukaryotic Cell ◽

Structure Activity ◽

Aliphatic Ketones ◽

Ic50 Values ◽

Central Nervous Systems ◽

Dual Inhibition ◽

Potential Inhibitors

Based on the broad spectrum of biological activity of hydrazide–hydrazones, trifluoromethyl compounds, and clinical usage of cholinesterase inhibitors, we investigated hydrazones obtained from 4-(trifluoromethyl)benzohydrazide and various benzaldehydes or aliphatic ketones as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). They were evaluated using Ellman’s spectrophotometric method. The hydrazide–hydrazones produced a dual inhibition of both cholinesterase enzymes with IC50 values of 46.8–137.7 µM and 19.1–881.1 µM for AChE and BuChE, respectively. The majority of the compounds were stronger inhibitors of AChE; four of them (2-bromobenzaldehyde, 3-(trifluoromethyl)benzaldehyde, cyclohexanone, and camphor-based 2o, 2p, 3c, and 3d, respectively) produced a balanced inhibition of the enzymes and only 2-chloro/trifluoromethyl benzylidene derivatives 2d and 2q were found to be more potent inhibitors of BuChE. 4-(Trifluoromethyl)-N’-[4-(trifluoromethyl)benzylidene]benzohydrazide 2l produced the strongest inhibition of AChE via mixed-type inhibition determined experimentally. Structure–activity relationships were identified. The compounds fit physicochemical space for targeting central nervous systems with no apparent cytotoxicity for eukaryotic cell line together. The study provides new insights into this CF3-hydrazide–hydrazone scaffold.

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Nitric Oxide Inhibitory Activity of Xanthones from the Green Fruits of Cratoxylum formosum ssp. pruniflorum

Australian Journal of Chemistry ◽

10.1071/ch10193 ◽

2010 ◽

Vol 63 (11) ◽

pp. 1550 ◽

Cited By ~ 15

Author(s):

Nawong Boonnak ◽

Achjana Khamthip ◽

Chatchanok Karalai ◽

Suchada Chantrapromma ◽

Chanita Ponglimanont ◽

...

Keyword(s):

Nitric Oxide ◽

Antibacterial Activity ◽

Inhibitory Activity ◽

Spectroscopic Methods ◽

Gram Negative Bacteria ◽

Gram Negative ◽

X Ray ◽

X Ray Crystallography ◽

Ic50 Values ◽

Mic Value

Three new xanthones, pruniflorone M-O (1–3), and a new xanthonolignoid, 3-methoxy-5′-demethoxycadensin G (4), were isolated from the green fruits of Cratoxylum formosum ssp. pruniflorum along with three known xanthones (5–7) and a known flavonoid (8). Their structures were elucidated by spectroscopic methods and the structure of 1 was also determined by X-ray crystallography. Compounds 2 and 7 showed potent nitric oxide inhibitory activity with IC50 values of 4.4 and 4.3 μM, respectively. Moreover, 7 also showed strong antibacterial activity against both Gram-positive and Gram-negative bacteria with an MIC value of 4.67 μg mL–1.

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Thioester-Containing Benzoate Derivatives with α-Glucosidase Inhibitory Activity from the Deep-Sea-Derived Fungus Talaromyces indigoticus FS688

Marine Drugs ◽

10.3390/md20010033 ◽

2021 ◽

Vol 20 (1) ◽

pp. 33

Author(s):

Mingqiong Li ◽

Saini Li ◽

Jinhua Hu ◽

Xiaoxia Gao ◽

Yanlin Wang ◽

...

Keyword(s):

Inhibitory Activity ◽

Deep Sea ◽

Spectroscopic Analysis ◽

X Ray Diffraction ◽

Docking Analysis ◽

X Ray ◽

Structure Activity ◽

Ic50 Value ◽

Ic50 Values ◽

Benzoate Derivatives

Eurothiocins C–H (1–6), six unusual thioester-containing benzoate derivatives, were isolated from the deep-sea-derived fungus Talaromyces indigoticus FS688 together with a known analogue eurothiocin A (7). Their structures were elucidated through spectroscopic analysis and the absolute configurations were determined by X-ray diffraction and ECD calculations. In addition, compound 1 exhibited significant inhibitory activity against α-glucosidase with an IC50 value of 5.4 μM, while compounds 4 and 5 showed moderate effects with IC50 values of 33.6 and 72.1 μM, respectively. A preliminary structure–activity relationship is discussed and a docking analysis was performed.

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In Silico and In Vitro Structure–Activity Relationship of Mastoparan and Its Analogs

Molecules ◽

10.3390/molecules27020561 ◽

2022 ◽

Vol 27 (2) ◽

pp. 561

Author(s):

Prapenpuksiri Rungsa ◽

Steve Peigneur ◽

Nisachon Jangpromma ◽

Sompong Klaynongsruang ◽

Jan Tytgat ◽

...

Keyword(s):

Antibacterial Activity ◽

Biological Activity ◽

Hemolytic Activity ◽

In Silico ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Helical Conformation ◽

Structure Activity ◽

Wide Range ◽

Α Helix

Antimicrobial peptides are an important class of therapeutic agent used against a wide range of pathogens such as Gram-negative and Gram-positive bacteria, fungi, and viruses. Mastoparan (MpVT) is an α-helix and amphipathic tetradecapeptide obtained from Vespa tropica venom. This peptide exhibits antibacterial activity. In this work, we investigate the effect of amino acid substitutions and deletion of the first three C-terminal residues on the structure–activity relationship. In this in silico study, the predicted structure of MpVT and its analog have characteristic features of linear cationic peptides rich in hydrophobic and basic amino acids without disulfide bonds. The secondary structure and the biological activity of six designed analogs are studied. The biological activity assays show that the substitution of phenylalanine (MpVT1) results in a higher antibacterial activity than that of MpVT without increasing toxicity. The analogs with the first three deleted C-terminal residues showed decreased antibacterial and hemolytic activity. The CD (circular dichroism) spectra of these peptides show a high content α-helical conformation in the presence of 40% 2,2,2- trifluoroethanol (TFE). In conclusion, the first three C-terminal deletions reduced the length of the α-helix, explaining the decreased biological activity. MpVTs show that the hemolytic activity of mastoparan is correlated to mean hydrophobicity and mean hydrophobic moment. The position and spatial arrangement of specific hydrophobic residues on the non-polar face of α-helical AMPs may be crucial for the interaction of AMPs with cell membranes.

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α-Glucosidase Inhibitory Activity of Cycloartane-Type Triterpenes Isolated from Indonesian Stingless Bee Propolis and Their Structure–Activity Relationship

Pharmaceuticals ◽

10.3390/ph12030102 ◽

2019 ◽

Vol 12 (3) ◽

pp. 102 ◽

Cited By ~ 7

Author(s):

Niken Pujirahayu ◽

Debu Kumar Bhattacharjya ◽

Toshisada Suzuki ◽

Takeshi Katayama

Keyword(s):

Inhibitory Activity ◽

Antioxidant Activities ◽

Stingless Bee ◽

Structure Activity Relationships ◽

Glucosidase Inhibitor ◽

Structure Activity ◽

Glucosidase Inhibitors ◽

Ic50 Values ◽

New Type ◽

Treatment Of Diabetes

This study reports on the antioxidant activity and α-glucosidase inhibitory activity of five cycloartane-type triterpenes isolated from Indonesian stingless bee (Tetragonula sapiens Cockerell) propolis and their structure–activity relationships. The structure of the triterpenes was determined to include mangiferolic acid (1), Cycloartenol (2), ambonic acid (3), mangiferonic acid (4), and ambolic acid (5). The inhibitory test results of all isolated triterpenes against α-glucosidase showed a high potential for inhibitory activity with an IC50 range between 2.46 and 10.72 µM. Among the compounds tested, mangiferonic acid (4) was the strongest α-glucosidase inhibitor with IC50 2.46 µM compared to the standard (–)-epicatechin (1991.1 µM), and also had antioxidant activities with IC50 values of 37.74 ± 6.55 µM. The study on the structure–activity relationships among the compounds showed that the ketone group at C-3 and the double bonds at C-24 and C-25 are needed to increase the α-glucosidase inhibitory activity. The carboxylic group at C-26 is also more important for increasing the inhibitory activity compared with the methyl group. This study provides an approach to help consider the structural requirements of cycloartane-type triterpenes from propolis as α-glucosidase inhibitors. An understanding of these requirements is deemed necessary to find a new type of α-glucosidase inhibitor from the cycloartane-type triterpenes or to improve those inhibitors that are known to help in the treatment of diabetes.

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Antioxidant and Antibacterial Activity of Sulfonamides Derived from Carvacrol: A Structure-Activity Relationship Study

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666191127144336 ◽

2020 ◽

Vol 20 (3) ◽

pp. 173-181 ◽

Cited By ~ 1

Author(s):

Aldo S. de Oliveira ◽

Luiz F. S. de Souza ◽

Ricardo J. Nunes ◽

Susana Johann ◽

David L. Palomino-Salcedo ◽

...

Keyword(s):

Antibacterial Activity ◽

Biological Activity ◽

Molecular Docking ◽

Small Molecule ◽

Bacterial Resistance ◽

Mechanisms Of Action ◽

New Drugs ◽

Structure Activity ◽

Relationship Study ◽

Antibacterial Potential

Background: Bacterial resistance to antibiotics is a growing problem in all countries and has been discussed worldwide. In this sense, the development of new drugs with antibiotic properties is highly desirable in the context of medicinal chemistry. Methodology: In this paper we investigate the antioxidant and antibacterial potential of sulfonamides derived from carvacrol, a small molecule with drug-like properties. Most sulfonamides had antioxidant and antibacterial potential, especially compound S-6, derived from beta-naphthylamine. Result: To understand the possible mechanisms of action involved in biological activity, the experimental results were compared with molecular docking data. Conclusion: This research allows appropriate discussion on the identified structure activity relationships.

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Halogen-Substituted Triazolethioacetamides as a Potent Skeleton for the Development of Metallo-β-Lactamase Inhibitors

Molecules ◽

10.3390/molecules24061174 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1174 ◽

Cited By ~ 1

Author(s):

Yilin Zhang ◽

Yong Yan ◽

Lufan Liang ◽

Jie Feng ◽

Xuejun Wang ◽

...

Keyword(s):

Antibiotic Resistance ◽

Inhibitory Activity ◽

Docking Studies ◽

Hydroxyl Group ◽

Inhibition Kinetics ◽

Ic50 Value ◽

Lactam Antibiotic ◽

Value Range ◽

Ic50 Values ◽

Enzyme Inhibition Kinetics

Metallo-β-lactamases (MβLs) are the target enzymes of β-lactam antibiotic resistance, and there are no effective inhibitors against MβLs available for clinic so far. In this study, thirteen halogen-substituted triazolethioacetamides were designed and synthesized as a potent skeleton of MβLs inhibitors. All the compounds displayed inhibitory activity against ImiS with an IC50 value range of 0.032–15.64 μM except 7. The chlorine substituted compounds (1, 2 and 3) inhibited NDM-1 with an IC50 value of less than 0.96 μM, and the fluorine substituted 12 and 13 inhibited VIM-2 with IC50 values of 38.9 and 2.8 μM, respectively. However, none of the triazolethioacetamides exhibited activity against L1 at inhibitor concentrations of up to 1 mM. Enzyme inhibition kinetics revealed that 9 and 13 are mixed inhibitors for ImiS with Ki values of 0.074 and 0.27μM using imipenem as the substrate. Docking studies showed that 1 and 9, which have the highest inhibitory activity against ImiS, fit the binding site of CphA as a replacement of ImiS via stable interactions between the triazole group bridging ASP120 and hydroxyl group bridging ASN233.

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Hits-to-Lead Optimization of the Natural Compound 2,4,6-Trihydroxy-3-geranyl-acetophenone (tHGA) as a Potent LOX Inhibitor: Synthesis, Structure-Activity Relationship (SAR) Study, and Computational Assignment

Molecules ◽

10.3390/molecules23102509 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2509 ◽

Cited By ~ 1

Author(s):

Chean Ng ◽

Kamal Rullah ◽

Faridah Abas ◽

Kok Lam ◽

Intan Ismail ◽

...

Keyword(s):

Inhibitory Activity ◽

Inhibitory Concentration ◽

Alkyl Chain ◽

Kinetics Study ◽

Toxicity Prediction ◽

Structure Activity ◽

Ic50 Value ◽

Competitive Inhibitors ◽

Ic50 Values ◽

Sar Study

A new series of 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) analogues were synthesized and evaluated for their lipoxygenase (LOX) inhibitory activity. Prenylated analogues 4a–g (half maximal inhibitory concentration (IC50) values ranging from 35 μ M to 95 μ M) did not exhibit better inhibitory activity than tHGA (3a) (IC50 value: 23.6 μ M) due to the reduction in hydrophobic interaction when the alkyl chain length was reduced. One geranylated analogue, 3d, with an IC50 value of 15.3 μ M, exhibited better LOX inhibitory activity when compared to tHGA (3a), which was in agreement with our previous findings. Kinetics study showed that the most active analogue (3e) and tHGA (3a) acted as competitive inhibitors. The combination of in silico approaches of molecular docking and molecular dynamic simulation revealed that the lipophilic nature of these analogues further enhanced the LOX inhibitory activity. Based on absorption, distribution, metabolism, excretion, and toxicity (ADMET) and toxicity prediction by komputer assisted technology (TOPKAT) analyses, all geranylated analogues (3a–g) showed no hepatotoxicity effect and were biodegradable, which indicated that they could be potentially safe drugs for treating inflammation.

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Antibacterial activity of selected medicinal plants against multiple antibiotic resistant uropathogens: a study from Kolli Hills, Tamil Nadu, India

Beneficial Microbes ◽

10.3920/bm2010.0033 ◽

2011 ◽

Vol 2 (3) ◽

pp. 235-243 ◽

Cited By ~ 13

Author(s):

A. Narayanan ◽

S. Raja ◽

K. Ponmurugan ◽

S. Kandekar ◽

K. Natarajaseenivasan ◽

...

Keyword(s):

Antibacterial Activity ◽

Antibiotic Resistance ◽

Medicinal Plants ◽

Inhibitory Activity ◽

Tamil Nadu ◽

Tinospora Cordifolia ◽

Diffusion Method ◽

Asparagus Racemosus ◽

Kolli Hills ◽

Agar Disc

The increasing incidence of antibiotic resistance among bacterial pathogens necessitates medicinal plants as an alternate therapy in restricting the resistant infectious organisms. In this primitive study, the antibiotic resistance of organisms isolated from urinary tract infected patients was evaluated using the National Committee for Clinical Laboratory Standards (NCCLS) method and Multiple Antibiotic Resistance (MAR) index values, and the MAR values was also calculated for plant extracts. The 10 common medicinal plants collected from Kolli hills, Namakkal, south India were extracted using the chloroform, methanol, acetone, ethanol and saponification procedure. The efficacy of the extracts on the uropathogens was tested by agar disc diffusion method in order to analyse the inhibitory activity of plant extract on the organisms. Azadiracta indica A. Juss., Tinospora cordifolia (Wild.) and Euphorbia hirta Linn. exhibited high inhibitory activity against most of the 11 tested organisms followed by Cassia javanica Linn. and Phyllanthus niruri Linn. The maximum zone size of 46.3 mm was exhibited by methanol extract of P. niruri Linn. against Pseudomonas aeruginosa. Asparagus racemosus Willd. and Eupatorium triplinerve Vahl had the least activity against resistant pathogens. Saponified lipids of most of the plants exhibited maximum antibacterial activity. Among the tested organisms, P. aeruginosa and Staphylococcus epidermidis were the most susceptible and Serratia marcescens, Enterobacter cloaceae, Citrobacter koseri, and Citrobacter freundii were the least inhibited by most of the extracts of medicinal plants. It is concluded that revised antibiotic policies and more importantly the development of herbal medicine as an alternative may be incorporated in urological practice.

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Synthesis of the 4’-desmethoxy analogue of RU79115

Journal of the Serbian Chemical Society ◽

10.2298/jsc0411855m ◽

2004 ◽

Vol 69 (11) ◽

pp. 855-859 ◽

Cited By ~ 1

Author(s):

Branislav Musicki ◽

Anne-Marie Periers ◽

Nicole Tessot ◽

Michel Klich

Keyword(s):

Antibacterial Activity ◽

Biological Activity ◽

Inhibitory Activity ◽

Methoxy Group

The synthesis, and biological activity in vitro of the 4?-desmethoxy analogue (3) of RU 79115 (2) is described. Comparison of the biological activity of the two analogues clearly indicated the importance of the 4?-methoxy group in conferring good gyrase B inhibitory activity as well as antibacterial activity.

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