scholarly journals Design, Synthesis and Evaluation of N-pyrazinylbenzamides as Potential Antimycobacterial Agents

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2390 ◽  
Author(s):  
Jan Zitko ◽  
Alžběta Mindlová ◽  
Ondřej Valášek ◽  
Ondřej Jand’ourek ◽  
Pavla Paterová ◽  
...  
Keyword(s):  
Benzene Ring ◽  
Biological Activities ◽  
Clinical Importance ◽  
Antimycobacterial Activity ◽  
Substitution Pattern ◽  
Design Synthesis ◽  
Fungal Strains ◽  
Mycobacterium Tuberculosis H37rv ◽  
Homo And Lumo

Three series of N-(pyrazin-2-yl)benzamides were designed as retro-amide analogues of previously published N-phenylpyrazine-2-carboxamides with in vitro antimycobacterial activity. The synthesized retro-amides were evaluated for in vitro growth inhibiting activity against Mycobacterium tuberculosis H37Rv (Mtb), three non-tuberculous mycobacterial strains (M. avium, M. kansasii, M. smegmatis) and selected bacterial and fungal strains of clinical importance. Regarding activity against Mtb, most N-pyrazinylbenzamides (retro-amides) possessed lower or no activity compared to the corresponding N-phenylpyrazine-2-carboxamides with the same substitution pattern. However, the active retro-amides tended to have lower HepG2 cytotoxicity and better selectivity. Derivatives with 5-chloro substitution on the pyrazine ring were generally more active compared to their 6-cloro positional isomers or non-chlorinated analogues. The best antimycobacterial activity against Mtb was found in N-(5-chloropyrazin-2-yl)benzamides with short alkyl (2h: R2 = Me; 2i: R2 = Et) in position 4 of the benzene ring (MIC = 6.25 and 3.13 µg/mL, respectively, with SI > 10). N-(5-Chloropyrazin-2-ylbenzamides with hydroxy substitution (2b: R2 = 2-OH; 2d: R2 = 4-OH) on the benzene ring or their acetylated synthetic precursors possessed the broadest spectrum of activity, being active in all three groups of mycobacterial, bacterial and fungal strains. The substantial differences in in silico calculated properties (hydrogen-bond pattern analysis, molecular electrostatic potential, HOMO and LUMO) can justify the differences in biological activities between N-pyrazinylbenzamides and N-phenylpyrazine-2-carboxamides.

Benzoylthioureas: Design, Synthesis and Antimycobacterial Evaluation

2020 ◽  
Vol 16 (1) ◽  
pp. 93-103
Author(s):  
Tiago O. Brito ◽  
Lethícia O. Abreu ◽  
Karen M. Gomes ◽  
Maria C.S. Lourenço ◽  
Patricia M.L. Pereira ◽  
...  
Keyword(s):  
Benzene Ring ◽  
Biological Activities ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
New Drugs ◽  
Design Synthesis ◽  
Thiourea Derivatives ◽  
Structural Modifications ◽  
General Series ◽  
Wide Range

Background: New drugs and strategies to treat tuberculosis (TB) are urgently needed. In this context, thiourea derivatives have a wide range of biological activities, including anti-TB. This fact can be illustrated with the structure of isoxyl, an old anti-TB drug, which has a thiourea as a pharmacophore group. Objective: The aim of this study is to describe the synthesis and the antimycobacterial activity of fifty-nine benzoylthioureas derivatives. Methods: Benzoylthiourea derivatives have been synthesized and evaluated for their activity against Mycobacterium tuberculosis using the MABA assay. After that, a structure-activity relationship study of this series of compounds has been performed. Results and Discussion: Nineteen compounds exhibited antimycobacterial activity between 423.1 and 9.6 μM. In general, we observed that the presence of bromine, chlorine and t-Bu group at the para-position in benzene ring plays an important role in the antitubercular activity of Series A. These substituents were fixed at this position in benzene ring and other groups such as Cl, Br, NO2 and OMe were introduced in the benzoyl ring, leading to the derivatives of Series B. In general, Series B was less cytotoxic than Series A, which indicates that the presence of a substituent at benzoyl ring contributes to an improvement in both antimycobacterial activity and toxicity profiles. Conclusion: Compound 4c could be considered a good prototype to be submitted to further structural modifications in the search for new anti-TB drugs, since it is 1.8 times more active than the first line anti-TB drug ethambutol and 0.65 times less active than isoxyl.

scholarly journals Design, synthesis and antimycobacterial evaluation of some new azaheterocycles with the 4,7-phenanthroline skeleton. Part VI

2016 ◽  
Vol 81 (2) ◽  
pp. 133-140 ◽  
Author(s):  
Matarneh Al ◽  
Catalina Ciobanu ◽  
Ionel Mangalagiu ◽  
Ramona Danac
Keyword(s):  
Antimycobacterial Activity ◽  
Alkylation Reaction ◽  
Design Synthesis ◽  
1H And 13C Nmr ◽  
Mycobacterium Tuberculosis H37rv ◽  
13C Nmr Analysis ◽  
New Compounds ◽  
Feasible Study ◽  
Influence Of Substituents

A feasible study concerning the synthesis, structure and in vitro antimycobacterial evaluation of new 4,7-phenanthroline derivatives is reported. The preparation is straight and efficient, involving an N-alkylation reaction of 4,7-phenanthroline. The structure of the new compounds have been proved by elemental and spectral (IR, 1H and 13C NMR) analysis. The in vitro antimycobacterial evaluation of five synthesized compounds was investigated against Mycobacterium tuberculosis H37Rv under aerobic conditions. A certain influence of substituents from the para position of the benzoyl moiety was observed, the 4,7-phenanthrolin-4-ium salt substituted with (p)chloro-benzoyl showing the most pronounced antimycobacterial activity.

Design, synthesis and biological activities of pyrrole-3-carboxamide derivatives as EZH2 (enhancer of zeste homologue 2) inhibitors and anticancer agents

2020 ◽  
Vol 44 (6) ◽  
pp. 2247-2255
Author(s):  
Qifan Zhou ◽  
Lina Jia ◽  
Fangyu Du ◽  
Xiaoyu Dong ◽  
Wanyu Sun ◽  
...  
Keyword(s):  
Biological Activity ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Activity Assay ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Enhancer Of Zeste

A novel series of pyrrole-3-carboxamides targeting EZH2 have been designed and synthesized. The structure–activity relationships were summarized by combining with in vitro biological activity assay and docking results.

scholarly journals Design, Synthesis and In Vitro Experimental Validation of Novel TRPV4 Antagonists Inspired by Labdane Diterpenes

Marine Drugs ◽  
2020 ◽  
Vol 18 (10) ◽  
pp. 519
Author(s):  
Sarah Mazzotta ◽  
Gabriele Carullo ◽  
Aniello Schiano Moriello ◽  
Pietro Amodeo ◽  
Vincenzo Di Marzo ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Biological Activities ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Design Synthesis ◽  
Cellular Assays ◽  
Transient Receptor ◽  
Trpv4 Channel

Labdane diterpenes are widespread classes of natural compounds present in variety of marine and terrestrial organisms and plants. Many of them represents “natural libraries” of compounds with interesting biological activities due to differently functionalized drimane nucleus exploitable for potential pharmacological applications. The transient receptor potential channel subfamily V member 4 (TRPV4) channel has recently emerged as a pharmacological target for several respiratory diseases, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Inspired by the labdane-like bicyclic core, a series of homodrimane-derived esters and amides was designed and synthesized by modifying the flexible tail in position 1 of (+)-sclareolide, an oxidized derivative of the bioactive labdane-type diterpene sclareol. The potency and selectivity towards rTRPV4 and hTRPV1 receptors were assessed by calcium influx cellular assays. Molecular determinants critical for eliciting TRPV4 antagonism were identified by structure-activity relationships. Among the selective TRPV4 antagonists identified, compound 6 was the most active with an IC50 of 5.3 μM. This study represents the first report of semisynthetic homodrimane TRPV4 antagonists, selective over TRPV1, and potentially useful as pharmacological tools for the development of novel TRPV4 channel modulators.

scholarly journals ONE-POT SYNTHESIS OF 2,4,5-TRIARYLIMIDAZOLES FROM KETO-OXIMES: CHARACTERIZATION AND EVALUATION OF ANTIMICROBIAL ACTIVITY

2019 ◽  
pp. 263-270
Author(s):  
KRANTHI KUMAR T ◽  
SREENIVASULU R
Keyword(s):  
Antimicrobial Activity ◽  
Biological Activities ◽  
Antimicrobial Properties ◽  
Antimycobacterial Activity ◽  
Diffusion Method ◽  
Current Investigation ◽  
One Pot ◽  
Fungal Strains ◽  
Aryl Aldehydes ◽  
Agar Disc

Background and Objective: Imidazole scaffold is pervasive in pharmaceuticals and it possesses diverse type of biological activities, especially triarylimidazole derivatives are biologically prominent molecules which inspired the current investigation. The objective of the work is to synthesize 15 novel 2,4,5-triarylimidazole derivatives and evaluate their antimicrobial and antimycobacterial activity against selected bacterial and fungal strains. Methods: The title compounds 2,4,5-triaryl-imidazole were synthesized from the corresponding aryl aldehydes and keto-oximes through the cyclization to N-hydroxyimidazoles and reduced thermally to the different imidazole derivatives. Agar disc diffusion method is employed for the antimicrobial and antimycobacterial studies. Results: Fifteen novel 2,4,5-triarylimidazoles were synthesized in adequate yields and characterization of the molecules was done by detailed spectral analysis using advanced analytical support. Results disclosed that all the synthesized compounds were exhibiting antimicrobial properties. Compounds 3h, 3g, 3b, and 3m were stated to possess potent antimicrobial properties in the given bacterial and fungal strains. Conclusion: The current investigation results support the antimicrobial and antimycobacterial activity of the synthesized 2,4,5-triarylimidazole derivatives. Further, research is necessary to explore the mechanism involved in the antimicrobial activity.

scholarly journals ANTIMICROBIAL, CYTOTOXIC AND HEMOLYTIC ACTIVITIES OF MARINE ALGAE-ASSOCIATED FUNGAL ISOLATES IN VIETNAM

2019 ◽  
Vol 18 (4) ◽  
pp. 406-412
Author(s):  
Hoang Kim Chi ◽  
Tran Thi Hong Ha ◽  
Le Huu Cuong ◽  
Tran Thi Nhu Hang ◽  
Nguyen Dinh Tuan ◽  
...  
Keyword(s):  
Natural Products ◽  
Human Cancer ◽  
Biological Activities ◽  
Breast Adenocarcinoma ◽  
Cytotoxic Activities ◽  
Marine Microorganisms ◽  
Fungal Strains ◽  
Fungal Isolates ◽  
Fungal Extracts

In the context of sources for natural products discovery are going scarcer, exploiting biotechnologically potential compounds from marine microbial symbionts is considered a relatively new trend. In our study a total of fifteen fungal strains were isolated from marine algal samples belonging to species Kappaphycus cottonii, K. striatus, Gracilaria eucheumatoides and Betaphycus gelatinus collected in Nha Trang in 2017. The in vitro biological activities, including antimicrobial, cytotoxic and hemolytic activities of ethyl acetate extracts of the fungal strains were determined. From fifteen fungal extracts, six displayed antimicrobial activity against at least one test strain. At 20 μg.ml-1, four fungal extracts were found to express cytotoxic activity on two human cancer cell lines hepatocellular carcinoma (Hep-G2) and breast adenocarcinoma (MCF-7), with G. eucheumatoides being the source of the highest number of producer strains. Hemolytic activity was observed in rabbit erythrocytes under almost all fungal extracts’ effect. No apparent relationship was observed between the biological activities of fungal isolates. The biological assessments uncovered several fungal candidates, such as Bge-1.1, Kco-2.1 and Geu-1.1 with relatively potent antimicrobial and cytotoxic activities while expressing less hemolytic effect at concentrations from 20 μg.ml-1 to 200 μg.ml-1. The results evidenced the potential of exploiting natural products from associated marine microorganisms, especially those for the purpose of pharmaceutical applications.

scholarly journals Design, Synthesis, and Biological Activities of Novel 1,3,5-Trimethylpyrazole-Containing Malonamide Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 562 ◽  
Author(s):  
Qi-Bo Li ◽  
Min Liao ◽  
Qing Liu ◽  
Tong Feng ◽  
Zhi-Yuan Xu ◽  
...  
Keyword(s):  
Plutella Xylostella ◽  
Mass Spectra ◽  
Biological Activities ◽  
Aphis Craccivora ◽  
Moderate Activity ◽  
Tetranychus Cinnabarinus ◽  
Substitution Pattern ◽  
Design Synthesis ◽  
Structural Modifications ◽  
Insecticidal Activities

New 1,3,5-trimethylpyrazole-containing malonamide derivatives based on pyflubumide were designed, synthesized, and characterized using 1H-NMR, 13C-NMR, and high-resolution mass spectra (HRMS). The results of preliminary bioassays showed that the target compounds possessed good activities against Tetranychus cinnabarinus, Plutella xylostella, and Aphis craccivora. Most of the target compounds exhibited moderate to good acaricidal activity against Tetranychus cinnabarinus at a concentration of 400 µg/mL, and some showed moderate activity at a concentration of 200 µg/mL; in particular, compounds 8m and 8p exhibited 70.0% mortality. In addition, some of the target compounds exhibited good insecticidal activities against Plutella xylostella at a concentration of 200 µg/mL, especially compounds 8i and 8o, which achieved 100.0% mortality at a concentration of 100 µg/mL. Interestingly, some of the target compounds exhibited potent anti-aphid activity against Aphis craccivora at a concentration of 200 µg/mL; furthermore, compounds 8p and 8q demonstrated 100.0% anti-aphid activity at a concentration of 50 µg/mL. The preliminary analyses of the structure–activity relationships (SAR) indicated that the acaricidal and insecticidal activities varied significantly depending on the type of substituent and substitution pattern, which provides guidance for the further investigation of such structural modifications.

Design, Synthesis and Biological Evaluation of Anti-tuberculosis Agents based on Bedaquiline Structure

2020 ◽  
Vol 16 (5) ◽  
pp. 703-714
Author(s):  
Chengjun Wu ◽  
Jinghan Luo ◽  
Mengtong Wu ◽  
Fanzhen Meng ◽  
Zhiqiang Cai ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Atp Synthase ◽  
Docking Study ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Mycobacterium Tuberculosis H37rv ◽  
Inhibitory Activities ◽  
Relationship Of

Background: Bedaquiline is a novel anti-tuberculosis drug that inhibits Mycobacterial ATP synthase. However, studies have found that bedaquiline has serious side effects due to high lipophilicity. Recently, the complete structure of ATP synthase was first reported in the Journal of Science. Objective: The study aimed to design, synthesise and carry out biological evaluation of antituberculosis agents based on the structure of bedaquiline. Methods: The mode of action of bedaquiline and ATP synthase was determined by molecular docking, and a series of low lipophilic bedaquiline derivatives were synthesized. The inhibitory activities of bedaquiline derivatives towards Mycobacterium phlei 1180 and Mycobacterium tuberculosis H37Rv were evaluated in vitro. A docking study was carried out to elucidate the structureactivity relationship of the obtained compounds. The predicted ADMET properties of the synthesized compounds were also analyzed. Results: The compounds 5c3, 6a1, and 6d3 showed good inhibitory activities (MIC=15.62 ug.mL-1). At the same time, the compounds 5c3, 6a1, and 6d3 also showed good drug-like properties through molecular docking and ADMET properties prediction. Conclusion: The results of in vitro anti-tuberculosis activity assays, docking studies and ADMET predictions indicate that the synthesized compounds have potential antifungal activity, with compounds 6a1 being further optimized and developed as lead compounds.

scholarly journals Synthesis of Tetrahydro-2H-[1,3,5]thiadiazine-5-(4-pyridylcarboxamido)-2-thione with antitubercular activity

2004 ◽  
Vol 72 (1) ◽  
pp. 35-41 ◽  
Author(s):  
D. Sriram ◽  
K. Jyothi Mallika ◽  
P. Yogeeswari
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Therapeutic Use ◽  
Tuberculosis H37rv ◽  
Mycobacterium Tuberculosis H37rv ◽  
Radiometric System ◽  
Elemental Analyses ◽  
Derivatives Of

3-Substituted-5-(4-pyridylcarboxamide)tetrahydro-2H-[1,3,5]thiadizine-2-thione derivatives (1-9) were synthesized as derivatives of isoniazid (INH) to overcome the resistance developed with its therapeutic use. The structures were confirmed by their spectral and elemental analyses data. These derivatives revealed higher lipophilicity compared with INH. The antimycobacterial activity of the synthesized compounds and INH was evaluated in vitro against Mycobacterium tuberculosis H37Rv at 6.25 µg/ml in BACTEC 12B medium using the BACTEC 460 radiometric system. The derivatives exhibited antitubercular activity.

scholarly journals Investigation of local anesthetic and antimycobacterial activity of Ottonia martiana Miq. (Piperaceae)

2015 ◽  
Vol 87 (4) ◽  
pp. 1991-2000 ◽  
Author(s):  
MIRIAM M. CUNICO ◽  
HERBERT A. TREBIEN ◽  
FÁBIO C. GALETTI ◽  
OBDULIO G. MIGUEL ◽  
MARILIS D. MIGUEL ◽  
...  
Keyword(s):  
Local Anesthetic ◽  
Ethanolic Extract ◽  
Antimycobacterial Activity ◽  
Topical Administration ◽  
Experimental Models ◽  
Selectivity Index ◽  
Analgesic Action ◽  
Mycobacterium Tuberculosis H37rv

ABSTRACT Ottonia martiana is a plant popularly known in Brazil by the use for toothache. Ethanolic extract (EE), hexane fraction (HF), dichloromethane fraction (DF) and piperovatine obtained from O. martiana were assayed in vitro and in vivo. The acute toxicity of EE was determined, and LD50 values of 164.5 and 65.0 mg/kg by the oral and intraperitoneal routes, respectively, indicated a high toxicity for EE in vivo, explaining its popular use by topical administration only. A local anesthetic-like effect of EE and its fractions was observed in experimental models using pain induction, and such effect involved an analgesic action. The antimycobacterial activity of EE, HF, DF and piperovatine was evaluated against Mycobacterium tuberculosis H37Rv ATCC 27924. EE, HF, DF, and piperovatine showed a potential antimycobacterial effect with MICs of 16.0, 62.0, 62.0 and 8.0 μg/mL, respectively. Piperovatine was more effective than the EE or the other fractions. The selectivity index (SI=IC50/MIC) values calculated for EE, HF, DF and piperovatine based on the MICs and the cytotoxicity against J774 macrophages (IC50 by MTT assay) revealed values of 6.43, 2.34, 1.5 and 9.66, respectively.

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