Synthesis, docking and evaluation of novel fused pyrimidine compounds as possible lead compounds with antibacterial and antitumor activities

Rami Y. Morjan; Amany F. El-Hallaq; Jannat N. Azarah; Ihab M. Almasri; Mazen M. Alzaharna; Mariam R. Al-Reefi; Ian Beadham; Omar S. Abu-Teim; Abdelraouf A. Elmanama; Adel M. Awadallah; James Raftery; John M. Gardiner

doi:10.1016/j.molstruc.2023.135754

Synthesis, docking and evaluation of novel fused pyrimidine compounds as possible lead compounds with antibacterial and antitumor activities

Rami Y. Morjan, Amany F. El-Hallaq, Jannat N. Azarah, Ihab M. Almasri, Mazen M. Alzaharna, Mariam R. Al-Reefi, Ian Beadham, Omar S. Abu-Teim, Abdelraouf A. Elmanama, Adel M. Awadallah, James Raftery, John M. Gardiner

Research output: Contribution to journal › Article › peer-review

Abstract

Reaction of a series of hydrazonoyl chlorides with substituted aminopyrimidines afforded good selectivity in most cases leading either to formation of new imidazo[1,2-a]pyrimidine derivatives, or regioisomeric hydrazonamide adducts. The compounds were evaluated for antibacterial and anticancer activities. Screening against 'E. Coli', 'P. aeruginosa', 'S. aureus', 'S. epidermidis', 'B. subtilis' and 'K. rhizophila' did identify several different compound types with MIC of 0.1-0.4 mg/mL. Anticancer evaluation against a HeLa cell line identified one imidazo[1,2-a]pyrimidine lead. An 'in silico' target fishing analysis suggest three possible high value protein targets, Tankyrase-2 (Tank-2), Cyclin-dependent kinase (CDK2) and Epidermal growth factor tyrosine kinase receptor (EGFR), with modelling fit against co-crystallized known ligands. This provides a new structural family lead for further investigation of molecular targets and potential SAR activity development.

Original language	English
Journal	Journal of Molecular Structure
Volume	1288
Issue number	135754
Early online date	14 May 2023
DOIs	https://doi.org/10.1016/j.molstruc.2023.135754
Publication status	Published - 15 Sept 2023

Bibliographical note

Note: This work was supported by The World Academy of Sciences for the Advancement of Science in Developing Countries (TWAS) through financial support to A. M. Awadallah, R. Y. Morjan, I. M. Almasri and M. M. Alzaharna [grant no. 16-490-RG/CHE/AF/AC_G-FR3240293296] and to J. N. Azarah [scholarship no. 16-490 RG/CHE/AF/AC_G-FR3240293296]. EPSRC for NMR instrumention [grant no. EP/K039547/1].

Keywords

Chemistry

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10.1016/j.molstruc.2023.135754

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https://doi.org/10.1016/j.molstruc.2023.135754

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Morjan, R. Y., El-Hallaq, A. F., Azarah, J. N., Almasri, I. M., Alzaharna, M. M., Al-Reefi, M. R., Beadham, I., Abu-Teim, O. S., Elmanama, A. A., Awadallah, A. M., Raftery, J., & Gardiner, J. M. (2023). Synthesis, docking and evaluation of novel fused pyrimidine compounds as possible lead compounds with antibacterial and antitumor activities. Journal of Molecular Structure, 1288(135754). https://doi.org/10.1016/j.molstruc.2023.135754

@article{e89f8c3ca1614042a5ba1a7900cd2e42,

title = "Synthesis, docking and evaluation of novel fused pyrimidine compounds as possible lead compounds with antibacterial and antitumor activities",

abstract = "Reaction of a series of hydrazonoyl chlorides with substituted aminopyrimidines afforded good selectivity in most cases leading either to formation of new imidazo[1,2-a]pyrimidine derivatives, or regioisomeric hydrazonamide adducts. The compounds were evaluated for antibacterial and anticancer activities. Screening against 'E. Coli', 'P. aeruginosa', 'S. aureus', 'S. epidermidis', 'B. subtilis' and 'K. rhizophila' did identify several different compound types with MIC of 0.1-0.4 mg/mL. Anticancer evaluation against a HeLa cell line identified one imidazo[1,2-a]pyrimidine lead. An 'in silico' target fishing analysis suggest three possible high value protein targets, Tankyrase-2 (Tank-2), Cyclin-dependent kinase (CDK2) and Epidermal growth factor tyrosine kinase receptor (EGFR), with modelling fit against co-crystallized known ligands. This provides a new structural family lead for further investigation of molecular targets and potential SAR activity development.",

keywords = "Chemistry",

author = "Morjan, \{Rami Y.\} and El-Hallaq, \{Amany F.\} and Azarah, \{Jannat N.\} and Almasri, \{Ihab M.\} and Alzaharna, \{Mazen M.\} and Al-Reefi, \{Mariam R.\} and Ian Beadham and Abu-Teim, \{Omar S.\} and Elmanama, \{Abdelraouf A.\} and Awadallah, \{Adel M.\} and James Raftery and Gardiner, \{John M.\}",

note = "Note: This work was supported by The World Academy of Sciences for the Advancement of Science in Developing Countries (TWAS) through financial support to A. M. Awadallah, R. Y. Morjan, I. M. Almasri and M. M. Alzaharna [grant no. 16-490-RG/CHE/AF/AC\_G-FR3240293296] and to J. N. Azarah [scholarship no. 16-490 RG/CHE/AF/AC\_G-FR3240293296]. EPSRC for NMR instrumention [grant no. EP/K039547/1].",

year = "2023",

month = sep,

day = "15",

doi = "10.1016/j.molstruc.2023.135754",

language = "English",

volume = "1288",

journal = "Journal of Molecular Structure",

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Morjan, RY, El-Hallaq, AF, Azarah, JN, Almasri, IM, Alzaharna, MM, Al-Reefi, MR, Beadham, I, Abu-Teim, OS, Elmanama, AA, Awadallah, AM, Raftery, J & Gardiner, JM 2023, 'Synthesis, docking and evaluation of novel fused pyrimidine compounds as possible lead compounds with antibacterial and antitumor activities', Journal of Molecular Structure, vol. 1288, no. 135754. https://doi.org/10.1016/j.molstruc.2023.135754

TY - JOUR

T1 - Synthesis, docking and evaluation of novel fused pyrimidine compounds as possible lead compounds with antibacterial and antitumor activities

AU - Morjan, Rami Y.

AU - El-Hallaq, Amany F.

AU - Azarah, Jannat N.

AU - Almasri, Ihab M.

AU - Alzaharna, Mazen M.

AU - Al-Reefi, Mariam R.

AU - Beadham, Ian

AU - Abu-Teim, Omar S.

AU - Elmanama, Abdelraouf A.

AU - Awadallah, Adel M.

AU - Raftery, James

AU - Gardiner, John M.

N1 - Note: This work was supported by The World Academy of Sciences for the Advancement of Science in Developing Countries (TWAS) through financial support to A. M. Awadallah, R. Y. Morjan, I. M. Almasri and M. M. Alzaharna [grant no. 16-490-RG/CHE/AF/AC_G-FR3240293296] and to J. N. Azarah [scholarship no. 16-490 RG/CHE/AF/AC_G-FR3240293296]. EPSRC for NMR instrumention [grant no. EP/K039547/1].

PY - 2023/9/15

Y1 - 2023/9/15

N2 - Reaction of a series of hydrazonoyl chlorides with substituted aminopyrimidines afforded good selectivity in most cases leading either to formation of new imidazo[1,2-a]pyrimidine derivatives, or regioisomeric hydrazonamide adducts. The compounds were evaluated for antibacterial and anticancer activities. Screening against 'E. Coli', 'P. aeruginosa', 'S. aureus', 'S. epidermidis', 'B. subtilis' and 'K. rhizophila' did identify several different compound types with MIC of 0.1-0.4 mg/mL. Anticancer evaluation against a HeLa cell line identified one imidazo[1,2-a]pyrimidine lead. An 'in silico' target fishing analysis suggest three possible high value protein targets, Tankyrase-2 (Tank-2), Cyclin-dependent kinase (CDK2) and Epidermal growth factor tyrosine kinase receptor (EGFR), with modelling fit against co-crystallized known ligands. This provides a new structural family lead for further investigation of molecular targets and potential SAR activity development.

AB - Reaction of a series of hydrazonoyl chlorides with substituted aminopyrimidines afforded good selectivity in most cases leading either to formation of new imidazo[1,2-a]pyrimidine derivatives, or regioisomeric hydrazonamide adducts. The compounds were evaluated for antibacterial and anticancer activities. Screening against 'E. Coli', 'P. aeruginosa', 'S. aureus', 'S. epidermidis', 'B. subtilis' and 'K. rhizophila' did identify several different compound types with MIC of 0.1-0.4 mg/mL. Anticancer evaluation against a HeLa cell line identified one imidazo[1,2-a]pyrimidine lead. An 'in silico' target fishing analysis suggest three possible high value protein targets, Tankyrase-2 (Tank-2), Cyclin-dependent kinase (CDK2) and Epidermal growth factor tyrosine kinase receptor (EGFR), with modelling fit against co-crystallized known ligands. This provides a new structural family lead for further investigation of molecular targets and potential SAR activity development.

KW - Chemistry

U2 - 10.1016/j.molstruc.2023.135754

DO - 10.1016/j.molstruc.2023.135754

M3 - Article

SN - 0022-2860

VL - 1288

JO - Journal of Molecular Structure

JF - Journal of Molecular Structure

IS - 135754

ER -

Synthesis, docking and evaluation of novel fused pyrimidine compounds as possible lead compounds with antibacterial and antitumor activities

Abstract

Bibliographical note

Keywords

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