Design, synthesis, anticancer activity and molecular docking studies of new benzimidazole derivatives bearing 1,3,4-oxadiazole moieties as potential thymidylate synthase inhibitors

Almalki, Abdulraheem S. A.; Nazreen, Syed; Elbehairi, Serag Eldin I.; Asad, Mohammad; Shati, Ali A.; Alfaifi, Mohammad Y.; Alhadhrami, A.; Elhenawy, Ahmed A.; Alorabi, Ali Q.; Asiri, Abdullah M.; Alam, Mohammad Mahboob

doi:10.1039/d2nj01980a

Cited by 21 publications

(18 citation statements)

References 46 publications

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“…The reactive intermediates 2–5 were synthesized using our previously reported methods with minor modifications. 32 Eugenol ( 1 ), on reaction with ethyl bromoacetate using potassium carbonate in dry acetone, yielded compound 2 (90%), which after reaction with hydrazine hydrate afforded compound 3 (88%). An alcoholic solution of compound 3 in KOH was treated with carbon disulfide at 0–30 °C and then refluxed, followed by acidification using concentrated hydrochloric acid, to yield the key intermediate 4 .…”

Section: Resultsmentioning

confidence: 99%

“…The reported TS inhibitor 5-fluorouracil (5-FU) was stabilized at the active site through various amino acid residues (SER216, ASN226, ARG50, ARG215, GLY217, CYS195, GLY222, HIS256, ARG175, ASP218, and ARG176). 32 The self-docking was used as a prior docking calculation to generate the docked pose. Then, the induced-fit-docking was applied to generate the final pose which was minimized using the OPLS force field.…”

Section: Resultsmentioning

confidence: 99%

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Design, synthesis and biological evaluation of new eugenol derivatives containing 1,3,4-oxadiazole as novel inhibitors of thymidylate synthase

et al. 2023

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Design, synthesis and biological evaluation of new eugenol derivatives containing 1,3,4-oxadiazole as novel inhibitors of thymidylate synthase

et al. 2023

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“…The in silico toxicity prediction of compounds 10 and 13 were carried out by pkCSM software [ 42 ], and the results are shown in Table S1 . It was observed that compounds 10 and 13 were less toxic compared to the standard drug erlotinib; the maximum tolerated dose for humans for compounds 10 and 13 was 0.3 and 0.125 mg/kg/day, respectively, which are much higher than the maximum dose for erlotinib (0.002 mg/kg/day).…”

Section: Resultsmentioning

confidence: 99%

Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation

et al. 2022

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In the current study, new benzimidazole-based 1,3,4-oxadiazole derivatives have been synthesized and characterized by NMR, IR, MS, and elemental analysis. The final compounds were screened for cytotoxicity against MDA-MB-231, SKOV3, and A549 cell lines and EGFR for inhibitory activities. Compounds 10 and 13 were found to be the most active against all the tested cell lines, comparable to doxorubicin, and exhibited significant inhibition on EGFR kinase, with IC50 0.33 and 0.38 μM, respectively, comparable to erlotinib (IC50 0.39 μM). Furthermore, these two compounds effectively suppressed cell cycle progression and induced cell apoptosis in MDA-MB-231, SKOV3, and A549 cell lines. The docking studies revealed that these compounds showed interactions similar to erlotinib at the EGFR site. It can be concluded that the synthesized molecules effectively inhibit EGFR, can arrest the cell cycle, and may trigger apoptosis and therefore, could be used as lead molecules in the development of new anticancer agents targeting EGFR kinase.

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“…The anticancer activity was evaluated on two mammalian cell lines, Huh-7 cells (Hepatocellular) and HeLa (Cervical) which were obtained from the American Type Culture Collection (ATCC, Rockville, MD) whereas MRC-5 (Normal human Lung fibroblast cells), were obtained from VACSERA Tissue Culture Unit, Egypt. It was performed according to previously published work [28] using doxorubicin as a positive reference drug.…”

Section: Anticancer Activitymentioning

confidence: 99%

HPLC Profile, Anticancer, Anti-inflammatory and Antioxidant Activities of Euphorbia inarticulata Ethanolic Extract

Alghamdi¹,

Ali²,

Alam³

et al. 2023

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Antioxidants, in addition to protection against oxidative stress, also possess anti-inflammatory and anticancer potentials. In this work, the ethanolic extract (EE) of Euphorbia inarticulata has been evaluated for antioxidant, anti-inflammatory and anticancer activities. The antioxidant activity showed that EE significantly scavenges DPPH (IC 50 = 54.56 ± 2.38 µg/ml) and H 2 O 2 (77.44 ± 2.76 µg/ml), whereas ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC) were found to be 100.93 ± 4.15 µg/ml and 46.72 ± 3.86 mg gallic acid equi/gm, respectively. The EE exhibited significant inhibition on COX-1 (IC 50 79.84µg/ml) and protein denaturation (IC 50 57.6 µg/ml), compared to indomethacin and diclofenac, respectively. Furthermore, EE was found to be effective in killing Huh-7 and HeLa cancerous cells with IC 50 104.62 (SI 2.36) and 145.11 µg/ml (SI 1.7), respectively, while doxorubicin displayed IC 50 0.71 (Huh-7) and 2.63 µg/ml (HeLa), whereas it was safe on normal MRC-5 cells. The HPLC analysis showed the presence of ellagic acid, caffeic acid, gallic acid, syringic acid, cinnamic acid and catechol which may be responsible for the promising antioxidant, anti-inflammatory and anticancer potentials exerted by the ethanolic extract of E. inarticulata. These results conclude that Euphorbia inarticulata ethanolic extract has anti-inflammatory and anticancer effects by triggering oxidative stress.

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Design, synthesis, anticancer activity and molecular docking studies of new benzimidazole derivatives bearing 1,3,4-oxadiazole moieties as potential thymidylate synthase inhibitors

Abstract: The present work describes the synthesis and anticancer activity of new benzimidazole derivatives bearing 1,3,4-oxadiazoles as thymidylate synthase inhibitors. The newly synthesized molecules were confirmed by NMR, mass, FT-IR and...

Cited by 21 publications

References 46 publications

Design, synthesis and biological evaluation of new eugenol derivatives containing 1,3,4-oxadiazole as novel inhibitors of thymidylate synthase

Design, synthesis and biological evaluation of new eugenol derivatives containing 1,3,4-oxadiazole as novel inhibitors of thymidylate synthase

Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation

HPLC Profile, Anticancer, Anti-inflammatory and Antioxidant Activities of Euphorbia inarticulata Ethanolic Extract

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