Synthesis, Biological Profile, and Molecular Docking of Some New BisImidazole Fused Templates and Investigation of Their Cytotoxic Potential as Anti-tubercular and/or Anticancer Prototypes

2020 ◽  
Vol 17 ◽  
Author(s):  
Refaie M. Kassab ◽  
Sobhi M. Gomha ◽  
Zeinab A. Muhammad ◽  
Ahmed S. El-khouly
Keyword(s):  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Phenacyl Bromide ◽  
Antitumor Activities ◽  
Reference Drug ◽  
Imidazole Derivatives ◽  
Fused Heterocycles ◽  
Lung Carcinoma Cell Line ◽  
Bromide Derivative ◽  
New Compounds

Background: There is a great need to discover more drugs with antimycobacterial activities to fight lung cancer and tuberculosis (two of the deadliest diseases world-wide). To our knowledge, the present study is the first to report antimycobacterial activity of imidazole-fused heterocycles. Objective: Construction of some bis-imidazole fused heterocycles with potential anti-tubercular and/or potent antitumor activities. Method: A series of bis-imidazole fused derivatives 6-8 and 13-16 was constructed using bis-phenacyl bromide derivative 2 as a synthetic platform. Compound 2 was also used to access bis-quinoxaline 20, bis-benzothiazine derivatives 23, and bisthiazolopyrimidine derivatives 26. The new bis-imidazole derivatives were evaluated for their anticancer activity against lung carcinoma cell line (A-549) using Cisplatin as a reference drug. The new compounds were also screened for their antitubercular activity against M. tuberculosis (ATCC 25177) using Isoniazid as a reference drug. Result: Among the new bis-imidazole derivatives, three examples showed remarkable antitumor activities while five other compounds showed high antimycobacterial activity. Conclusion: A novel series of bis-imidazole fused heterocycles was developed. Multiple prototypes of this new series showed remarkable anti-tubercular and/or potent antitumor activities.

Synthesis, Antimicrobial and Antitumor Evaluations of a New Class of Thiazoles Substituted on the Chromene Scaffold

2019 ◽  
Vol 19 (20) ◽  
pp. 1717-1725 ◽  
Author(s):  
Dina H. Elnaggar ◽  
Naglaa A. Abdel Hafez ◽  
Huda R.M. Rashdan ◽  
Nayera A.M. Abdelwahed ◽  
Hanem M. Awad ◽  
...  
Keyword(s):  
Human Cell Line ◽  
Diffusion Method ◽  
Cytotoxic Activities ◽  
Antitumor Activities ◽  
Reference Drug ◽  
New Class ◽  
Excellent Activity ◽  
Thiosemicarbazide Derivatives ◽  
New Compounds

Background & Objective: A new series of thiazoles substituted on the chromene scaffold were prepared by facial approaches starting from (E)-1-(2,3-Dihydrochromen-4-ylidene)thiosemicarbazide derivatives (2a,b). The thiosemicarbazides (2a,b) were reacted with a series of α-halo carbonyl compounds to give the corresponding rhodanine analogues and reacted also with C-acetyl-or Cethoxy- N-hydrazonoyl chlorides to afford the corresponding tri- and tetra-substituted hybrid hydrazinyl thiazole substituted chromenes. Methods: The newly synthesized compounds were screened for their in vitro antimicrobial and antitumor activities by agar diffusion method and MTT assay, respectively. Results: The results of the antimicrobial activity revealed that some of the new compounds exhibited excellent activity against pathogenic microorganism; Candida albicans compared with Ciprofloxacin and nystatin, as the reference drugs. : All of the tested compounds exhibited significant cytotoxic activities comparable to that of the reference drug; Doxorubicin® (on HCT116 (colorectal carcinoma human cell line).

scholarly journals SYNTHESIS AND ANTITUBERCULAR ACTIVITY OF PIPERIDINE AND MORPHOLINE 1, 8 NAPHTHYRIDINE ANALOGUES

2016 ◽  
Vol 8 (12) ◽  
pp. 252 ◽  
Author(s):  
Muwaffag Badawneh ◽  
Jalal Aljamal
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inhibitory Concentration ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Significant Activity ◽  
Reference Drug ◽  
Novel Drugs ◽  
Elemental Analyses ◽  
Antimycobacterial Agents

<p><strong>Objective: </strong>The search for new, potentially useful antimycobacterial agents. In continuation with our previous screening for the discovery of novel drugs for tuberculosis, a new series of 1,8-naphthyridines derivatives were synthesized and evaluated <em>in vitro </em>for antimycobacterial activity against <em>Mycobacterium tuberculosis </em>H37Rv.</p><p><strong>Methods: </strong>Several 4-morpholinomethyl-1.8-naphthyridine derivatives have been synthesized in excellent yields. The synthesized compounds were characterized by spectroscopic methods as well as elemental analyses. They were screened for their antimycobacterial activity. The growth was monitored radiometrically in 7H12 broth with the BACTEC 460 TB system. The minimum inhibitory concentration (MIC) was determined for compounds that demonstrated ≥ 90% growth inhibition in the primary screening.</p><p><strong>Results: </strong>The obtained data suggested that all compounds showed significant activity against <em>Mycobacterium tuberculosis </em>H37Rv<em> </em>compared to the standard reference drug. Analogues (6-11) having heterocyclic groups in position 7 were the most potent of those we tested.</p><p><strong>Conclusion: </strong>These findings clearly identify the 1,8-naphthyridine analogue (10) with a 6-amino-2-(4'-methoxy benzylamine-4-morpholinomethyl-7-morpholino-substituent as promising anti-tubercular agents possessing significant activity against <em>Mycobacterium tuberculosis </em>H37Rv</p>

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.

Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors

2020 ◽  
Vol 75 (9-10) ◽  
pp. 353-362
Author(s):  
Begüm Nurpelin Sağlık ◽  
Ahmet Mücahit Şen ◽  
Asaf Evrim Evren ◽  
Ulviye Acar Çevik ◽  
Derya Osmaniye ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Biological Effects ◽  
Docking Studies ◽  
Benzimidazole Derivatives ◽  
Binding Modes ◽  
Reference Drug ◽  
In Silico Studies ◽  
New Compounds ◽  
Mcf 7

AbstractInhibition of aromatase enzymes is very important in the prevention of estrogen-related diseases and the regulation of estrogen levels. Aromatase enzyme is involved in the final stage of the biosynthesis of estrogen, in the conversion of androgens to estrogen. The development of new compounds for the inhibition of aromatase enzymes is an important area for medicinal chemists in this respect. In the present study, new benzimidazole derivatives have been designed and synthesized which have reported anticancer activity in the literature. Their anticancer activity was evaluated against human A549 and MCF-7 cell lines by MTT assay. In the series, concerning MCF-7 cell line, the most potent compounds were the 4-benzylpiperidine derivatives 2c, 2g, and 2k with IC50 values of 0.032 ± 0.001, 0.024 ± 0.001, and 0.035 ± 0.001 µM, respectively, compared to the reference drug cisplatin (IC50 = 0.021 ± 0.001 µM). Then, these compounds were subject to further in silico aromatase enzyme inhibition assays to determine the possible binding modes and interactions underlying their activity. Thanks to molecular docking studies, the effectiveness of these compounds against aromatase enzyme could be simulated. Consequently, it has been found that these compounds can be settled very properly to the active site of the aromatase enzyme.

scholarly journals Synthesis of Novel Sulfamethaoxazole 4-Thiazolidinone Hybrids and Their Biological Evaluation

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3570 ◽  
Author(s):  
Mashooq A. Bhat ◽  
Mohamed A. Al-Omar ◽  
Ahmed M. Naglah ◽  
Azmat Ali Khan
Keyword(s):  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Biological Evaluation ◽  
Oral Drug ◽  
Drug Candidates ◽  
Cyclocondensation Reaction ◽  
Aryl Aldehyde ◽  
Hct 116 ◽  
Mcf 7

A search for potent antitubercular agents prompted us to design and synthesize sulfamethaoxazole incorporated 4-thiazolidinone hybrids (7a–l) by using a cyclocondensation reaction between 4-amino-N-(5-methylisoxazol-3-yl)benzenesulfonamide (4), aryl aldehyde (5a–l), and mercapto acetic acid (6) resulting in good to excellent yields. All the newly synthesized 4-thiazolidinone derivatives were screened for their in vitro antitubercular activity against M. Bovis BCG and M. tuberculosis H37Ra (MTB) strains. The compounds 7d, 7g, 7i, 7k, and 7l revealed promising antimycobacterial activity against M. Bovis and MTB strains with IC90 values in the range of 0.058–0.22 and 0.43–5.31 µg/mL, respectively. The most active compounds were also evaluated for their cytotoxicity against MCF-7, HCT 116, and A549 cell lines and were found to be non-cytotoxic. Moreover, the synthesized compounds were also analyzed for ADME (absorption, distribution, metabolism, and excretion) properties and showed potential as good oral drug candidates.

One-pot synthesis of new triazole-sucrose derivatives via click chemistry and evaluation of their antitubercular activity

2016 ◽  
Vol 22 (4) ◽  
Author(s):  
Khaoula Hajlaoui ◽  
Ahlem Guesmi ◽  
Naoufel Ben Hamadi ◽  
Moncef Msaddek
Keyword(s):  
Click Chemistry ◽  
Copper Nanoparticles ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Dipolar Cycloaddition ◽  
One Pot ◽  
Effective Catalyst ◽  
One Pot Synthesis

AbstractReadily prepared copper nanoparticles are an effective catalyst for 1,3-dipolar cycloaddition of carbohydrate azide and a variety of alkynes that furnishes the corresponding 1,2,3-triazole-sucrose derivatives in excellent yields. Products were screened for their antimycobacterial activity against

A preliminary investigation of anticancer activity of novel benzothiazole derivatives against A549 lung carcinoma cell line

2017 ◽  
Vol 42 (5) ◽  
Author(s):  
Leyla Yurttaş ◽  
Betül Kaya Çavuşoğlu ◽  
Arda Sever ◽  
Gülşen Akalin Çiftçi
Keyword(s):  
Cell Line ◽  
Preliminary Investigation ◽  
Flow Cytometric Analysis ◽  
Chemotherapeutic Agents ◽  
Oral Drug ◽  
Benzothiazole Derivatives ◽  
Lung Carcinoma Cell Line ◽  
A549 Lung Carcinoma Cell ◽  
New Compounds ◽  
A549 Lung

AbstractObjective(s):In this study, it was aimed to synthesize new chemotherapeutic agents based on known antiproliferative properties of benzothiazol-2-amine moiety. The antitumor activity of the newly synthesized compounds was determined against A549 lung cancer cell lines.Methods:Eighteen compounds were obtained by two steps synthetic route. The anticancer potency of the compounds were detected using MTT assay and flow cytometric analysis on A549 cell line. Some physicochemical properties of the compounds were calculated, virtually.Results:Compounds 15 and 18 showed the highest cytotoxic activity even than cisplatin. Also, it was determined that compound 18 caused 19.1% (early and late) apoptosis whereas cisplatin caused 21.6% (early and late).Conclusion:Considering the calculated virtual data, eighteen new compounds were found within the boundaries of Lipinski rule of five to be an oral drug. Besides, the most potent compounds 15 and 18 were detected that both have 1-methylbenzimidazole structure, and also methoxy and ethoxy substituents on benzothiazole ring.

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 Synthesis, antimicrobial and anti-cancer activities of some new N-ethyl, N-benzyl and N-benzoyl-3-indolyl heterocycles

2012 ◽  
Vol 62 (2) ◽  
pp. 157-179 ◽  
Author(s):  
Eslam El-Sawy ◽  
Adel Mandour ◽  
Khaled Mahmoud ◽  
Inas Islam ◽  
Heba Abo-Salem
Keyword(s):  
Hydrazine Hydrate ◽  
Hydroxylamine Hydrochloride ◽  
Reference Drug ◽  
Highly Active ◽  
Anti Cancer ◽  
Hct 116 ◽  
New Compounds ◽  
Substituted 1 ◽  
Isoxazole Derivatives

Synthesis, antimicrobial and anti-cancer activities of some newN-ethyl,N-benzyl andN-benzoyl-3-indolyl heterocyclesA series of 1-(N-substituted-1H-indol-3-yl)-3-arylprop-2-ene-1-ones (2a, b-4a, b) were prepared and allowed to react with urea, thiourea or guanidine to give pyrimidine derivatives5a, b-13a, b. Reaction of2a, b-4a, bwith ethyl acetoacetate in the presence of a base gave cyclohexanone derivatives14a, b-16a, b. Reaction of the latter compounds with hydrazine hydrate afforded indazole derivatives17a, b-19a, b. On the other hand, reaction of2a, b-4a, bwith some hydrazine derivatives, namely hydrazine hydrate, acetyl hydrazine, phenylhydrazine and benzylhydrazine hydrochloride, led to the formation of pyrazole derivatives20a, b-31a, b. Moreover, reaction of2a, b-4a, bwith hydroxylamine hydrochloride gave isoxazole derivatives32a, b-34a, b. The newly synthesized compounds were tested for their antimicrobial activity and showed that 4-(N-ethyl-1H-indol-3-yl)-6-(p-chlorophenyl)-pyrimidine-2-amine (11b) was the most active of all the test compounds towardsCandida albicanscompared to the reference drug cycloheximide. Eighteen new compounds, namely pyrimidin-2(1H)-ones5a, b-7a, b, pyrimidin-2(1H)-thiones8a, b-10a, band pyrimidin-2-amines11a, b-13a, bderivatives, were tested for theirin vitroantiproliferative activity against HEPG2, MCF7 and HCT-116 cancer cell lines. 4-(N-ethyl-1H-indol-3-yl)-6-(p-methoxyphenyl)-pyrimidin-2-amine (11a)was found to be highly active withIC50of 0.7 μmol L-1.

Sign in / Sign up

Export Citation Format

Share Document