Quantitative analysis of hydrogen and chalcogen bonds in two pyrimidine-5-carbonitrile derivatives, potential DHFR inhibitors: an integrated crystallographic and theoretical study

Al-Wahaibi, Lamya H.; Chakraborty, Kushumita; Al-Shaalan, Nora Hamad; Majeed, Mohamed Yehya Annavi Syed; Blacque, Olivier; Al-Mutairi, Aamal A.; El-Emam, Ali A.; Percino, M. Judith; Thamotharan, Subbiah

doi:10.1039/d0ra07215j

Cited by 7 publications

(3 citation statements)

References 66 publications

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“…Toward more validation for the occurrence of noncovalent interactions, QTAIM analysis was implemented. , Diagrams of QTAIM relevant to the optimized ZF 5 /XF 3 O 2 /AeF 2 O 3 ···pyridine/NCH complexes are graphed in Figure . The corresponding topological parameters, encompassing the ∇ 2 ρ b , H b , and ρ b , were computed and are enrolled in Table .…”

Section: Resultsmentioning

confidence: 99%

σ-Hole Site-Based Interactions within Hypervalent Pnicogen, Halogen, and Aerogen-Bearing Molecules with Lewis Bases: A Comparative Study

Ibrahim,

Mahmoud,

Shehata

et al. 2024

ACS Omega

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Hole site-based interactions in the trigonal bipyramidal geometrical structure of hypervalent pnicogen, halogen, and aerogenbearing molecules with pyridine and NCH Lewis bases (LBs) were comparatively examined. In this respect, the ZF 5 •••, XF 3 O 2 •••, and AeF 2 O 3 •••LB complexes (where Z = As, Sb; X = Br, I; Ae = Kr, Xe; and LB = pyridine and NCH) were investigated. The electrostatic potential (EP) analysis affirmations outlined the occurrence of σ-holes on the systems under consideration with disparate magnitudes that increased according to the following order: AeF 2 O 3 < XF 3 O 2 < ZF 5 . In line with EP outcomes, the proficiency of σ-hole site-based interactions increased as the atomic size of the central atom increased with a higher favorability for the pyridine-based complexes over NCH-based ones. The interaction energy showed the most favorable negative values of −35.97, −44.53, and −56.06 kcal/mol for the XeF 2 O 3 •••, IF 3 O 2 •••, and SbF 5 •••pyridine complexes, respectively.The preferentiality pattern of the studied interactions could be explained as a consequence of (i) the dramatic rearrangement of ZF 5 molecules from the trigonal bipyramid geometry to the square pyramidal one, (ii) the significant and tiny deformation energy in the case of the interaction of XF 3 O 2 molecules with pyridine and NCH, respectively, and (iii) the absence of geometrical deformation within the AeF 2 O 3 •••pyridine and •••NCH complexes other than the XeF 2 O 3 •••pyridine one. Quantum theory of atoms in molecules and noncovalent interaction index findings reveal the partially covalent nature of most of the investigated interactions. Symmetry−adapted perturbation theory affirmations declared that the electrostatic component was the driving force beyond the occurrence of the considered interactions. The obtained findings will help in improving our understanding of the effect of geometrical deformation on intermolecular interactions.

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Section: Resultsmentioning

confidence: 99%

σ-Hole Site-Based Interactions within Hypervalent Pnicogen, Halogen, and Aerogen-Bearing Molecules with Lewis Bases: A Comparative Study

Ibrahim,

Mahmoud,

Shehata

et al. 2024

ACS Omega

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“…The 6-phenyl-2-thiouracil-5-carbonitrile derivatives 7a–d were obtained by prolonged heating of different aldehydes, thiourea, and ethyl cyanoacetate with K 2 CO 3 ( Scheme 3 ) 54 . Finally, compounds 7a – d were refluxed with the chloride derivative 2 in acetone using potassium carbonate to furnish the corresponding cyanothiouracils 8a – d ( Schemes 3 ).…”

Section: Resultsmentioning

confidence: 99%

New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study

Al‐Sanea

Hamdi

Mohamed

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione 4a–e , 1,3,4-thiadiazole aryl urea 6a–d, and cyanothiouracil moieties 8a–d was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, 4a was the most potent showing IC50 of 5.61, 7.92, and 3.84 µM, respectively. Furthermore, compounds 4e and 8a proved to have strong impact on breast cancer cell line with IC50 of 6.11 and 10.86 µM, respectively. The three compounds showed a good safety profile towards normal WI-38 cells. Flow cytometric analysis of the three compounds in MCF-7 cells revealed that compounds 4a and 4c inhibited cell population in the S phase, whereas 8a inhibited the population in the G1/S phase. The most promising compounds were subjected to a VEGFR-2 inhibitory assay where 4a emerged as the best active inhibitor of VEGFR-2 with IC50 91 nM, compared to 53 nM for SOR. In silico analysis showed that the three new hybrids succeeded to link to the active site like the co-crystallized inhibitor SOR.

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“…dipole, and others are calculated by GOLD, and all bond lengths below 3Aº[33]. Thesecompounds (7-10) and (20-25) are shown in Figure.…”

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confidence: 99%

Synthesis, Biological Activity, and Molecular Docking Studied of New Substituted Hydrazones

Nabel B. Ayrim,

Asim A. Balakit,

Souad J. Lafta

2023

J. K. Chem. Sci.

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Series of new hydrazones derived from different carboxylic acid hydrazides and aromatic aldehydes (7-10, 20-25) have been synthesized and characterized by spectral techniques (FT-IR, 1H NMR, 13C NMR, and Mass spectrometry). The target compounds are designed to have the different substituents at the para position for both parts of the structures (hydrazide and aldehyde parts. The synthesized compounds have been evaluated as antimicrobial agents by studying their biological activity against two bacteria strains Staphylococcus aureus and Staphylococcus epidermidis (as gram-positive bacteria), Escherichia coli and Klebsiella sp (as gram-negative bacteria), the antifungal activity was studied against Candida albicans fungi. The obtained results showed a moderate antimicrobial activity for the test compounds when compared with ampicillin. The synthesized compounds were also subjected to molecular docking studies which were carried out against the bacteria strain Staphylococcus aureus DHFR.

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Quantitative analysis of hydrogen and chalcogen bonds in two pyrimidine-5-carbonitrile derivatives, potential DHFR inhibitors: an integrated crystallographic and theoretical study

Abstract: Qualitative and quantitative analyses of hydrogen and chalcogen bonds in two pyrimidine-5-carbonitrile derivatives are described.

Cited by 7 publications

References 66 publications

σ-Hole Site-Based Interactions within Hypervalent Pnicogen, Halogen, and Aerogen-Bearing Molecules with Lewis Bases: A Comparative Study

σ-Hole Site-Based Interactions within Hypervalent Pnicogen, Halogen, and Aerogen-Bearing Molecules with Lewis Bases: A Comparative Study

New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study

Synthesis, Biological Activity, and Molecular Docking Studied of New Substituted Hydrazones

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