Synthesis, Anticancer Activity and Molecular Docking Studies of Hybrid Benzimidazole-1,3,4-Oxadiazol-2-<i>N</i>-Alkyl/Aryl Amines

Katikireddy, Ramamurthy; Marri, Srinivas; Kakkerla, Ramu; Krishna, M. P. S. Murali; Gandamalla, Durgaiah; Reddy, Y. V. R.

doi:10.1080/10406638.2021.1959352

Cited by 10 publications

(4 citation statements)

References 50 publications

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“…Furthermore, from previous studies, the conclusion that 1, 3, 4-oxadiazole ring-containing derivatives, when docked into EGFR usually form hydrogen bonds at the Thr830 and Asp831 positions suggests that these are two important positions that contribute to the inhibitory potential and significant cytotoxicity activity of this derivative. 50–53 In addition, several hydrophobic interactions have been observed with the amino acids Thr830, Asp831, Leu753, Leu764, Met742, Val702, Cys773, Leu694, Leu820, and Lys721. In the zerumbone 2-mercapto-1,3,4-oxadiazole hybrid series, particularly in compound 20a , there are two strong hydrogen bonds with the binding pocket residues at positions Phe699 and Gly700, along with other hydrophobic interactions as shown in Figure 4.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and cytotoxic activity evaluation of novel dihydroartemisinin and zerumbone conjugates with 2-mercapto-1,3,4-oxadiazoles as potential EGFR inhibitors

Tran,

Truong,

Nguyen

et al. 2023

Journal of Chemical Research

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Sixteen conjugates of dihydroartemisinin and zerumbone with 2-mercapto-1,3,4-oxadiazoles were synthesized and structurally elucidated by 1D NMR, 2D NMR, and HRMS spectra. The cytotoxic screening results showed that all the conjugates of dihydroartemisinin with 2-mercapto-1,3,4-oxadiazoles (19a-h) exhibited cytotoxic activity against two human cancer cell lines, HepG2 and LU-1, with the IC50 values ranging from 2.22 to 40.69 µM. Among dihydroartemisinin conjugates, conjugate 19b displayed the strongest activity against both HepG2 and LU-1 cell lines, with the IC50 values of 3.49 and 2.22 μM, respectively. The zerumbone conjugates (20a-h) expressed their cytotoxic activity stronger than that of 19a-h series, with IC50 values ranging from 1.54 to 2.00 µM. In addition, all 16 compounds exhibited an impressively inhibitory effect against EGFR tyrosine kinase with binding affinities ranging from −8.61 to −10.2 kcal/mol, higher than that of the erlotinib drug (−7.50 kcal/mol), a co-crystallized inhibitor of EGFR receptor. Both conjugates (19a and 20a) containing the 2-hydroxyphenyl-2mercapto-1,3,4-oxadiazole moiety had the best binding energies (−10.2 and −9.494 kcal/mol, respectively) on the EGFR tyrosine kinase. Furthermore, the potential interactions and binding patterns between the compounds and the relevant amino acid residues revealed the most significant contribution to amplifying their efficacy against this protein, according to docking studies, which identified both hydrogen bonds and hydrophobic contacts at the active site of the EGFR protein.

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Section: Resultsmentioning

confidence: 99%

Synthesis and cytotoxic activity evaluation of novel dihydroartemisinin and zerumbone conjugates with 2-mercapto-1,3,4-oxadiazoles as potential EGFR inhibitors

Tran,

Truong,

Nguyen

et al. 2023

Journal of Chemical Research

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“…Additionally, compound XX was less toxic against normal human embryonic kidney cell line HEK293 (IC50 = 37.25 µM) than Doxorubicin (IC50 = 6.40 µM). A molecular docking study showed a high affinity of the compound to the EGFR kinase site (PDB_ID: 4HJO) with the value of -8.6 Kcal/mol which is comparable to that of Doxorubicin (-8.9 Kcal/mol) [24] Additionally, hybrids XXIa-b showed promising anticancer activity against MCF-7 cell lines with IC50 equal to 1.53 μM and 2.08 μM, respectively compared to Doxorubicin (IC50 =1.45 μM). Moreover, the two compounds had higher binding affinity in EGFR (PDB 1M17) with binding energy equal to -8.42 kcal/mol and -8.45 kcal/mol kcal/mol, respectively than Erlotinib which had binding energy equal to -7.90 kcal/mol [25].…”

Section: XIImentioning

confidence: 92%

New Oxadiazole/ Benzimidazole Hybrids: Design, Synthesis, and Molecular Docking Studies.

Hagar

Abbas

Sayed

et al. 2023

Journal of advanced Biomedical and Pharmaceutical Sciences

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Five new oxadiazole/benzimidazole hybrids were designed and synthesized as EGFR inhibitors. The structure of the new compounds was confirmed with 1 H NMR and 13 C NMR as well as elemental analyses. Molecular docking studies were done to investigate their binding mode in ATP binding site of EGFR. The synthesized hybrids exhibited good binding in EGFR binding site. The thiol tautomers got better docking scores than thione ones. The docking scores of hybrids ranged from -7.4 kcal/mol to -8.7 kcal/mol which were comparable to that of the co-crystalized ligand Erlotinib (score = -9.7 kcal/mol). In silico physicochemical and pharmacokinetic properties prediction of them indicated that they have drug like properties.

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“…Huynh and his coworkers in 2020 [83] [84] reported benzimidazoles having oxadiazoles substances (270(a-j)) which are illustrated in Scheme 30. Applying the MTT test with doxorubicin as a standard against HeLa, MCF7, A549, and HEK293 cancerous cell lines for anticancer activities; the compound 270f showed remarkable activity toward HeLa, MCF-7, and A529 cell lines, with IC 50 values of 4.68 0.04; 4.16 0.07, and 5.40 ± 0.08 µM, respectively.…”

Section: S C H E M Ementioning

confidence: 99%

The medicinal panorama of benzimidazoles and their scaffolds as anticancer and antithrombotic agents: A review

Chalkappa,

Aralihalli,

Sudileti

et al. 2023

Archiv der Pharmazie

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Nitrogen‐containing heterocyclic scaffolds have become a prospective pharmacophore with therapeutic importance due to their biological similarities with natural and synthetic drugs. Among all nitrogen heterocyclic compounds, benzimidazoles and their derivatives are privileged molecules structurally akin to naturally available nucleotides, enabling them to intercommunicate with numerous biopolymers in biological systems. This reason enlightens modern researchers worldwide to assess their potential significance in the context of synthetic and biological chemistry. Therefore, it is crucial to merge the latest data with the prior documentation to apprehend the ongoing situation of the benzimidazole moiety in various therapeutic zones of research. The current work displays that the benzimidazole center is a versatile nucleus that offers the necessary data of synthetic alterations for pre‐existing compounds to provide new scaffolds to resist numerous therapeutic sectors, including those associated with anticancer and antithrombosis. Due to the potential significance of benzimidazoles, this review aims to emphasize the latest innovations in synthesizing several other notable benzimidazole substrates and their significant pharmacological prospects for the future, including anticancer and antithrombosis.

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Synthesis, Anticancer Activity and Molecular Docking Studies of Hybrid Benzimidazole-1,3,4-Oxadiazol-2-N-Alkyl/Aryl Amines

Cited by 10 publications

References 50 publications

Synthesis and cytotoxic activity evaluation of novel dihydroartemisinin and zerumbone conjugates with 2-mercapto-1,3,4-oxadiazoles as potential EGFR inhibitors

Synthesis and cytotoxic activity evaluation of novel dihydroartemisinin and zerumbone conjugates with 2-mercapto-1,3,4-oxadiazoles as potential EGFR inhibitors

New Oxadiazole/ Benzimidazole Hybrids: Design, Synthesis, and Molecular Docking Studies.

The medicinal panorama of benzimidazoles and their scaffolds as anticancer and antithrombotic agents: A review

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