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 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.

Pharmacologically potentials of different substituted coumarin derivatives

2019 ◽  
Author(s):  
Chem Int
Keyword(s):  
Benzene Ring ◽  
Bioactive Compounds ◽  
Biological Activities ◽  
Pharmacological Properties ◽  
Coumarin Derivatives ◽  
Wide Range ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Coumarin Compounds

Coumarin and its derivatives are widely spread in nature. Coumarin goes to agroup as benzopyrones, which consists of a benzene ring connected to a pyronemoiety. Coumarins displayed a broad range of pharmacologically useful profile.Coumarins are considered as a promising group of bioactive compounds thatexhibited a wide range of biological activities like anti-microbial, anti-viral,antiparasitic, anti-helmintic, analgesic, anti-inflammatory, anti-diabetic, anticancer,anti-oxidant, anti-proliferative, anti-convulsant, and antihypertensiveactivities etc. The coumarin compounds have immense interest due to theirdiverse pharmacological properties. In particular, these biological activities makecoumarin compounds more attractive and testing as novel therapeuticcompounds.

Advances in Triazole Synthesis from Copper-catalyzed Azide-alkyne Cycloadditions (CuAAC) Based on Eco-friendly Procedures

2019 ◽  
Vol 16 (2) ◽  
pp. 244-257 ◽  
Author(s):  
Marcus Vinicius Nora de Souza ◽  
Cristiane França da Costa ◽  
Victor Facchinetti ◽  
Claudia Regina Brandão Gomes ◽  
Paula Mázala Pacheco
Keyword(s):  
Biological Activities ◽  
Reaction Times ◽  
Water Extract ◽  
Fish Bone ◽  
New Drugs ◽  
Bone Powder ◽  
Wide Range ◽  
Recoverable Catalysts ◽  
Egg Shell ◽  
Work Up

Background: 1,2,3-triazoles are an important class of organic compounds and because of their aromatic stability, they are not easily reduced, oxidized or hydrolyzed in acidic and basic environments. Moreover, 1,2,3-triazole derivatives are known by their important biological activities and have drawn considerable attention due to their variety of properties. The synthesis of this nucleus, based on the click chemistry concept, through the 1,3-dipolar addition reaction between azides and alkynes is a well-known procedure. This reaction has a wide range of applications, especially on the development of new drugs. Methods: The most prominent eco-friendly methods for the synthesis of triazoles under microwave irradiation published in articles from 2012-2018 were reviewed. Results: In this review, we cover some of the recent eco-friendly CuAAC procedures for the click synthesis of 1,2,3-triazoles with remarks to new and easily recoverable catalysts, such as rhizobial cyclic β-1,2 glucan; WEB (water extract of banana); biosourced cyclosophoraose (CyS); egg shell powder (ESP); cyclodextrin (β- CD); fish bone powder; nanoparticle-based catalyst, among others. Conclusion: These eco-friendly procedures are a useful tool for the synthesis of 1,2,3-triazoles, providing many advantages on the synthesis of this class, such as shorter reaction times, easier work-up and higher yields when compared to classical procedures. Moreover, these methodologies can be applied to the industrial synthesis of drugs and to other areas.

Design, Synthesis, Anti-Proliferative Evaluation and Cell Cycle Analysis of Hybrid 2-Quinolones

2019 ◽  
Vol 19 (9) ◽  
pp. 1132-1140
Author(s):  
Heba A.E. Mohamed ◽  
Hossa F. Al-Shareef
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Cytotoxic Activities ◽  
Significant Group ◽  
Design Synthesis ◽  
Standard Drug ◽  
Wide Range

Background: Quinolones are a significant group of nitrogen heterocyclic compounds that exist in therapeutic agents, alkaloids, and synthetic small molecules that have important biological activities. A wide range of quinolones have been used as antituberculosis, antibacterial, anti-malarial, antifungal, anticonvulsant, anticancer agents and urease inhibitors. Methods: Ethyl 3,3-disubstituted-2-cyano propionates containing hybride quinolones derivatives were synthesized by the reaction of 1-amino-7-hydroxy-4-methylquinolin-2(1H)-one and its dibromo derivative with α, β-unsaturated carbonyl in ethanol. Results: A novel series of hybrid 2-quinolone derivatives was designed and synthesized. The compounds structures were confirmed using different spectroscopic methods and elemental analysis. The cytotoxic activities of all the compounds were assessed against HepG2 cell line in comparison with doxorubicin as a standard drug. Conclusion: Most compounds revealed superior anti-proliferative activity than the standard. Compound 4b, is the most active compound (IC50 = 0.39mM) compared with doxorubicin (IC50 = 9.23mM). DNA flow cytometric analysis of compound 4b showed cell cycle arrest at G2/M phase with a concomitant increase of cells in apoptotic phase. Dual annexin-V/ propidium iodide staining assay of compound 4b revealed that the selected candidate increased the apoptosis of HepG-2 cells more than control.

scholarly journals ChCl: Gly (DESs) Promote Environmentally Benign Synthesis of Xanthene Derivatives and Their Antitubercular Activity

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3667
Author(s):  
Mashooq A. Bhat ◽  
Ahmed M. Naglah ◽  
Siddique Akber Ansari ◽  
Hanaa M. Al-Tuwajiria ◽  
Abdullah Al-Dhfyan
Keyword(s):  
Reaction Times ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Environmentally Benign ◽  
Reaction Yield ◽  
Benign Synthesis ◽  
Xanthene Derivatives ◽  
Wide Range ◽  
Major Application

A ChCl: Gly (DESs) promoted environmentally benign method was developed for the first time using the reaction of aryl aldehydes and dimedone to give excellent yields of xanthene analogues. The major application of this present protocol is the use of green solvent, a wide range of substrate, short reaction times, ease of recovery, the recyclability of the catalyst, high reaction yield, and ChCl: Gly as an alternative catalyst and solvent. In addition to this, all the synthesized compounds were evaluated for their in vitro antimycobacterial activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. The compounds 3d, 3e, 3f, and 3j showed significant antitubercular activity against MTB and M. bovis strains with minimum inhibitory concentration (MIC) values of 2.5−15.10 µg/mL and 0.26–14.92 µg/mL, respectively. The compounds 3e, 3f, and 3j were found to be nontoxic against MCF-7, A549, HCT 116, and THP-1 cell lines. All the prepared compounds were confirmed by 1H NMR and 13C NMR analysis.

Identification of promising objects for the synthesis of thiosulphonate derivatives of benzoquinone and hydroquinone

2021 ◽  
Vol 4 (2) ◽  
pp. 47-53
Author(s):  
N. Y. Monka ◽  
◽  
N. E. Stadnytska ◽  
I. R. Buchkevych ◽  
K. O. Kaplia ◽  
...  
Keyword(s):  
Biological Activity ◽  
Biological Activities ◽  
Experimental Studies ◽  
New Drugs ◽  
Reduced Form ◽  
Free Form ◽  
Wide Range ◽  
On Line ◽  
Living Organisms ◽  
Derivatives Of

Benzoquinone and its reduced form hydroquinone belong to phenolic compounds and are found in living organisms in free form or in glycosides. They are active substances of some medicinal plants and have a pharmacological effect on the human body. Accordingly, their derivatives are important objects for chemical synthesis and development of new drugs. This article presents the findings of the structural design of substances with benzoquinone or hydroquinone fragment and sulfur-containing compound. By use of appropriate on-line programs a predictive screening of the biological activity and cytotoxicity of thiosulfonate derivatives of benzoquinone and hydroquinone has been conducted. It has been found that they have immense methodological potential to be synthesized by substances with a wide range of biological activities and a high value of probable activity, which substantiates the feasibility of conducting experimental studies on their biological activity, particularly anticancer.

Design, Synthesis and Evaluation of Aryloxybenzylidene Hydrazinyl-Benzoxazoles/Benzothiazoles Analogs as Antimycobacterial Agents

2020 ◽  
Vol 5 (3) ◽  
pp. 185-191
Author(s):  
G. Aruna ◽  
Ravindra Kulkarni ◽  
Baswaraj Machaa ◽  
Malathi Jojula ◽  
Shravan Gunda ◽  
...  
Keyword(s):  
Spectral Data ◽  
Condensation Reaction ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Molecular Hybridization ◽  
Design Synthesis ◽  
Antitubercular Drugs ◽  
Pantothenate Synthetase ◽  
Antimycobacterial Agents ◽  
Mic Value

Substituted 2-(2-(4-aryloxybenzylidene)hydrazinyl)benzothiazole/benzoxazoles series were designed through molecular hybridization and synthesized in condensation reaction of hydrazinylbenzothiazole/ benzoxazole with substituted aryloxy benzaldehydes. All the synthesized compounds were assigned structure based on spectral data and were evaluated for antimycobacterial activity. Among both benzothiazole and benzoxazole derivatives, the compounds 8f and 9e were found to show most potent antitubercular activity with MIC value of 0.89 and 0.92 μM which are on a par with those of standard antitubercular drugs. In order to know the binding interactions of all the compounds were docked within the mycobacterial pantothenate synthetase, which showed interactions with Asp88, Arg200, Ser196, Asn199, Met 195 and Lys 160 of pantothenate synthetase.

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.

Fastidious Anatomization of Biota Procured Compounds on Cancer Drug Discovery

2020 ◽  
Vol 21 (5) ◽  
pp. 354-363
Author(s):  
Anand Thirupathi ◽  
Chandra M. Shanmugavadivelu ◽  
Sampathkumar Natarajan
Keyword(s):  
Natural Products ◽  
Side Effects ◽  
Cancer Therapy ◽  
Biological Activities ◽  
Drug Approval ◽  
Current Treatment ◽  
New Drugs ◽  
Cancer Drug ◽  
Synthetic Drugs ◽  
Wide Range

Background: Natural products are the rootstock for identifying new drugs since ancient times. In comparison with synthetic drugs, they have abounding beneficial effects in bestowing protection against many diseases, including cancer. Cancer has been observed as a major threat in recent decades, and its prevalence is expected to increase over the next decades. Also, current treatment methods in cancer therapy such as radiation therapy and chemotherapy cause severe adverse side effects among the cancer population. Therefore, it is exigent to find a remedy without any side effects. Methods: In recent years, research has focused on obtaining naturally derived products to encounter this complication. The current pace of investigations, such as gene identification and advancement in combinatorial chemistry, leads to the aberrant access to a wide range of new synthetic drugs. In fact, natural products act as templates in structure predictions and synthesis of new compounds with enhanced biological activities. Results: Recent developments in genomics have established the importance of polymorphism, which implies that patients require different drugs for their treatment. This demands the discovery of a large number of drugs, but limited sources restrict the pharmaceutical industry to overcome these major obstacles. The use of natural products and their semisynthetic and synthetic analogues could alleviate these problems. However, the lack of standardization in terms of developing methods for evaluating the chemical composition, efficacy, isolation and international approval is still a major limitation in this field. In the past few years, several drug-approval authorities, including the FDA and WHO have allowed using these naturally derived compounds in humans. Conclusion: In this review, we described the use of some natural products from plant and marine sources in cancer treatment and shed some light on semi-synthetic and synthetic compounds derived from natural sources used in cancer therapy.

Current Pharmaceutical Aspects of Synthetic Quinoline Derivatives

2020 ◽  
Vol 20 ◽  
Author(s):  
Rukhsana Tabassum ◽  
Muhammad Ashfaq ◽  
Hiroyuki Oku
Keyword(s):  
Fungal Infections ◽  
Biological Activities ◽  
Chemical Properties ◽  
New Drugs ◽  
Quinoline Derivatives ◽  
Wide Range ◽  
Anti Cancer ◽  
Anti Fungal ◽  
Physical And Chemical ◽  
And Chemical Properties

Abstract:: Quinoline derivatives are considered as broad spectrum pharmacological compounds that exhibit wide range of biological activities. Integration of quinoline moiety can improve its physical and chemical properties and also pharmacological behavior. Due to its wide range of pharmaceutical applications it is very popular compound to design new drugs for treatment of multiple diseases like cancer, dengue fever, malaria, tuberculosis, fungal infections, AIDS, Alzheimer’s disease and diabetes . In this review our major focus is to pay attention on biological activities of quinoline compounds in treatment of these diseases such as, anti-viral, anti-cancer, anti-malarial, anti-bacterial, anti-fungal, anti-tubercular and anti-diabetic.

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