Design, synthesis, molecular docking of new lipophilic acetamide derivatives affording potential anticancer and antimicrobial agents

Ahmed, Hany E. A.; Ihmaid, Saleh; Omar, Abdelsattar M.; Shehata, Ahmed; Rateb, Heba S.; Zayed, Mohamed F.; Ahmed, Sahar; Elaasser, Mahmoud M.

doi:10.1016/j.bioorg.2017.11.019

Cited by 40 publications

(18 citation statements)

References 62 publications

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“…The minimal inhibitory and bactericidal concentrations (MIC) and (MBC) ] for the most active compounds 6b , 6c , 6d , 6f , 6i , 10a , and 10d , which are shown in Table and Figure , were in accordance with the results obtained in the primary inhibition zone screening. The thiazole derivatives inhibited the Gram ‐positive strain types at values range of MIC and MBC (1 – 6.8 μg/mL) slightly against Gram ‐negative types.…”

Section: Resultssupporting

confidence: 86%

Synthesis, Biological Evaluation, and Molecular Docking of Novel Thiazoles and [1,3,4]Thiadiazoles Incorporating Sulfonamide Group as DHFR Inhibitors

Riyadh

El-Motairi

Ahmed

et al. 2018

Chemistry & Biodiversity

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2-(1-{4-[(4-Methylphenyl)sulfonamido]phenyl}ethylidene)thiosemicarbazide (3) was exploited as a starting material for the synthesis of two novel series of 5-arylazo-2-hydrazonothiazoles 6a - 6j and 2-hydrazono[1,3,4]thiadiazoles 10a - 10d, incorporating sulfonamide group, through its reactions with appropriate hydrazonoyl halides. The structures of the newly synthesized products were confirmed by spectral and elemental analyses. Also, the antimicrobial, anticancer, and DHFR inhibition potency for two series of thiazoles and [1,3,4]thiadiazoles were evaluated and explained by molecular docking studies and SAR analysis.

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Section: Resultssupporting

confidence: 86%

Synthesis, Biological Evaluation, and Molecular Docking of Novel Thiazoles and [1,3,4]Thiadiazoles Incorporating Sulfonamide Group as DHFR Inhibitors

Riyadh

El-Motairi

Ahmed

et al. 2018

Chemistry & Biodiversity

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“…The 2,3-disubstituted-6-fluoro-3 H -quinazolin-4-ones ( 6 – 8 ) and ( 10a – g ) were subjected to cytotoxic screening using two types of breast cancer cell lines (MCF-7) and (MDA-MBA-231) using MTT assay [ 17 , 18 , 19 ]. The IC 50 values of screening are listed in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…20 µL of MTT was added to each well and incubated for 2 h before 200 µL DMSO was added. The absorbance was measured on an ELISA reader (Multiskan EX, Lab systems, Waltham, MA, USA) at wavelength of 570 nm [ 17 , 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…Other quinazolines yield their anticancer activity by inhibition of DNA repairing system or tubulin polymerization. There are many other derivatives have dual EGFR/tubulin polymerization inhibitors, like amide derivatives and quinoxalines [ 16 , 17 , 18 , 19 ]. Many efforts have been aimed at finding safe and potent molecules with the present chemotherapeutic agents [ 10 , 11 , 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, Cytotoxic Evaluation and Molecular Docking of New Fluoroquinazolinones as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects

Zayed

Ahmed

Ihmaid

et al. 2018

IJMS

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A series of new fluoroquinazolinone 6–8 and 10a–g derivatives was designed, prepared and screened for their in vitro cytotoxic activity against human cancer cell lines MCF-7 and MDA-MBA-231. Compounds 6 (IC50 = 0.35 ± 0.01 µM), 10f (IC50 = 0.71 ± 0.01 µM), 10d (IC50 = 0.89 ± 0.02 µM) and 10a (IC50 = 0.95 ± 0.01 µM) displayed broad spectrum anticancer activity better than the reference drug gefitinib (IC50 = 0.97 ± 0.02 µM) against MCF-7. Compounds 10e (IC50 = 0.28 ± 0.02 µM), 10d (IC50 = 0.38 ± 0.01 µM), 7 (IC50 = 0.94 ± 0.07 µM) and 10c (IC50 = 1.09 ± 0.01 µM) showed better activity than the reference gefitinib (IC50 = 1.30 ± 0.04 µM) against MDA-MBA-231. Moreover, EGFR and tubulin inhibition assays were performed for the highest active derivatives and showed remarkable results comparing to the reference drugs. In order to assess and explain their binding affinities, molecular docking simulation was studied against EGFR and tubulin binding sites. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated.

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“…As a result, there is an urgent need to discover and develop new classes of anticancer drugs to combat the growth of drug resistance [ 5 ]. Our literature survey revealed that quinoxalines and their fused analogs are attractive candidates in medicinal chemistry as they constitute the building blocks of a wide range of compounds possessing a numerous interesting biological properties such as anticancer [ 6 , 7 ], antihistaminic [ 8 ], antiviral [ 9 ], antimicrobial [ 10 , 11 , 12 ], antifungal [ 13 ] antitubercular [ 14 , 15 ] and anti-inflammatory effects [ 16 ]. Among the biologically active pharmacophores, amides have been associated with fascinating anticancer [ 17 ], antitubercular [ 18 , 19 ], anti-inflammatory [ 20 ] and imines are reported to have analgesic [ 21 ] properties.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Cytotoxic Evaluation of Novel Chalcone Derivatives Bearing Triazolo[4,3-a]-quinoxaline Moieties as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects

et al. 2017

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A series of hybrid of triazoloquinoxaline-chalcone derivatives 7a–k were designed, synthesized, fully characterized, and evaluated for their cytotoxic activity against three target cell lines: human breast adenocarcinoma (MCF-7), human colon carcinoma (HCT-116), and human hepatocellular carcinoma (HEPG-2). The preliminary results showed that some of these chalcones like 7b–c, and 7e–g exhibited significant antiproliferative effects against most of the cell lines, with selective or non-selective behavior, indicated by IC50 values in the 1.65 to 34.28 µM range. In order to investigate the mechanistic aspects of these active compounds, EGFR TK and tubulin inhibitory activities were measured as further biological assays. The EGFR TK assay results revealed that the derivatives 7a–c, 7e, and 7g could inhibit the EGFR TK in the submicromolar range (0.093 to 0.661 µM). Moreover, an antitubulin polymerization effect was noted for the active derivatives compared to the reference drug colchicine, with compounds 7e and 7g displaying 14.7 and 8.4 micromolar activity, respectively. Furthermore, a molecular docking study was carried out to explain the observed effects and the binding modes of these chalcones with the EGFR TK and tubulin targets.

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Design, synthesis, molecular docking of new lipophilic acetamide derivatives affording potential anticancer and antimicrobial agents

Cited by 40 publications

References 62 publications

Synthesis, Biological Evaluation, and Molecular Docking of Novel Thiazoles and [1,3,4]Thiadiazoles Incorporating Sulfonamide Group as DHFR Inhibitors

Synthesis, Biological Evaluation, and Molecular Docking of Novel Thiazoles and [1,3,4]Thiadiazoles Incorporating Sulfonamide Group as DHFR Inhibitors

Design, Synthesis, Cytotoxic Evaluation and Molecular Docking of New Fluoroquinazolinones as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects

Design, Synthesis and Cytotoxic Evaluation of Novel Chalcone Derivatives Bearing Triazolo[4,3-a]-quinoxaline Moieties as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects

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