In Silico Discovery of Novel CDK1 Inhibitors from Linum Species for Targeted Cancer Therapy

Enzyme	PDB ID	Classification	Organism	Expression system	Resolution	Method	TSW (kDA)	Chain
CDK1/Cks2	6GU7	Cell Cycle	Homo sapiens	Spodoptera frugiperda, Escherichia coli	2.75 Å	XRD	179.75	1) A, C, E, G 2) B, D, F, H
CDK1/cyclinB1/CKS2	5LQF	Transferase	Homo sapiens	Escherichia coli	2.06 Å	XRD	153.23	1) A, D 2) B, E 3) C, F

[i] PDB, Protein Data Bank; TSW, Total structure weight; Å, Angstrom; XRD, X-ray diffraction.

The crystal structure of 6GU7 in complex with AZD5438
a) Surface representation of the protein and
b) A close view of the substrate (in yellow) binding in pocket by hydrogen bonds (in green).

The crystal structure of 5LQF in complex with NU6102 (4SP).
Middle: Surface representation of the protein. Left: A close view of the substrate in receptor A.
Right: A close view of the substrate in receptor D, substrate (in yellow) and hydrogen bonds (in green).

Table 2.

Chemical compounds and physicochemical parameters of compounds identified by LC-HRMS/MS analysis in ethyl acetate extracts of L. numidicum (LN) and L. trigynum (LT).

Compounds Name	MW (g/mol)	Conse Log P_o/w	TPSA (Å²)	GI Abs	P-gp Sub	Lipinski	CYP3A4 inhibitor
6,4ʹ-dimethoxy- scutellarein-7-neohesperidoside	622.57	−0.01	227.2	low	Yes	No	No
8,3ʹ,4ʹ-trihydroxyflavone-7-O-6(6ʺ-O-p-coumaroyl)-β-d-glucopyranoside	594.52	1.15	216.58	low	No	No	No
Foliasalacioside B1	504.57	−0.57	175.37	low	No	No	No
Isovitexin 2ʺ-O-arabinoside	564.49	−1.26	239.9	low	yes	No	No
Luteolin-7,3ʹ-di-O-β-d-glucoside	610.52	−1.49	269.43	low	yes	No	No
Malvidin 3-O-β-galactoside	493.44	−0.74	191.67	low	No	No	yes
Olivil 4ʹ-O-β-d-glucoside	538.54	0.1	187.76	low	Yes	No	No
Rutin	610.52	−1.29	269.43	low	Yes	No	No
Vicenin-2 isomer 2	594.52	−1.98	271.2	low	No	No	No
Vicenin-2 isomer 3	594.52	−1.98	271.2	low	Yes	No	No
Violanthin	578.52	−1.43	250.97	low	Yes	No	No
Vitexin-2ʺ-rhamnoside	578.52	−0.99	239.97	low	Yes	No	No

[i] MW, Molecular weight; Conse log p_o/w, Consensus Log Partition Coefficient (octanol/water); TPSA, Topological Polar Surface Area; GI Abs, Gastrointestinal Absorption; P-gp Sub, P-glycoprotein Substrate; CYP3A4, Cytochrome. P450 3A4 inhibitor.

Table 3.

Chemical structures and physicochemical parameter of main proposed drugs for cancer treatment.

Drugs name	Pub chem ID	MW (g/mol)	Conse Log P_o/w	TPSA (Å²)	GI Abs	P-gp Sub	Lipinski	CYP3A4 inhibitor
Flavopiridol	44297210	401.8	2.78	94.14	high	Yes	Yes	Yes
Dinaciclib	46926350	396.49	1.84	91.15	high	Yes	Yes	No
AZD5438	16747683	371.46	2.51	98.15	high	Yes	Yes	No
NU6102 (4SP)	4566	402.47	2.22	144.26	Low	Yes	Yes	No
Indirubin	135398511	365.38	2.38	110.43	high	Yes	Yes	No
Roniciclib	45380979	430.44	3.74	116.57	Low	Yes	Yes	Yes
Podophyllotoxin	10607	414.41	2.28	92.68	high	No	Yes	Yes

Table 4.

Docking results of drugs under clinical test and reference ligands inhibitors.

	6GU7		5LQF receptor A		5LQF receptor D
Drugs and reference ligands	E score	RMSD	E score	RMSD	E score	RMSD
Flavopiridol	−7.4933	1.6222	−7.6560	2.0977	−7.5930	1.1823
Dinaciclib	−7.5641	2.9463	−8.6410	1.6370	−7.7471	2.7987
AZD5438	−6.7570	1.4343	−8.2058	1.1977	−7.6836	1.4969
NU6102 (4SP)	−7.0154	1.4603	−9.2294	1.8517	−8.7623	2.1990
Indirubin	−5.9587	1.17179	−6.5945	0.8525	−6.4472	0.8468
Roniciclib	−7.1375	1.75631	−8.9343	0.8115	−8.6737	2.6749
podophyllotoxin	−6.6977	2.1235	−7.6797	2.0758	−7.3931	2.1096

[i] E score, binding energy score (kcal/mol); RMSD, Root Mean Square Deviation (Å).

Table 5.

Results of docking of compounds identified in ethyl acetate extracts of L. numidicum and L. trigynum with 6GU7 and 5LQF targets

	6GU7		5LQF/A		5LQF/D
Ligands	E score	RMSD	E score	RMSD	E scrore	RMSD
6,4ʹ-dimethoxy-scutellarein-7-neohesperidoside	−8.7922	2.4460	−9.8332	1.4417	−9.6457	1.6701
8,3ʹ,4ʹ-trihydroxyflavone-7-O-6(6ʺ-O-p-coumaroyl)-β-d-glucopyranoside	−8.8836	1.5144	−9.8308	2.1867	−9.6374	2.0696
Foliasalacioside B1	−8.1466	2.2304	−7.9735	2.0343	−9.0780	1.5581
Isovitexin 2ʺ-O-arabinoside	−8.2867	2.2208	−8.7986	1.0639	−9.0273	1.3896
Luteolin-7,3ʹ-di-O-β-d-glucoside	−8.4639	1.5872	−9.7184	1.4914	−9.3306	2.0331
Malvidin 3-O-β-galactoside	−7.5680	1.7951	−8.7742	2.6041	−8.9311	1.8049
Olivil 4ʹ-O-β-d-glucoside	−8.0439	1.5787	−8.8431	2.1685	−8.5054	1.7226
Rutin	−8.5279	1.7807	−9.5872	2.1477	−9.1845	1.8575
Vicenin-2 isomer 2	−8.9413	1.3524	−9.7820	1.4479	−9.6997	1.1453
Vicenin-2 isomer 3	−8.5247	1.2757	−8.7863	1.8631	−9.6332	1.3865
Violanthin	−8.0624	1.2929	−9.1498	2.5548	−9.5624	1.5645
Vitexin-2ʺ-rhamnoside	−8.5079	2.4076	−8.6167	3.7997	−8.9943	1.4957

[i] E score, binding energy score (kcal/mol); RMSD, Root Mean Square Deviation (Å).

a) 2D and b) 3D interactions of vicenin-2 isomer 2 in the binding site of 6GU7. (in 3D: Ligand in purple, residues pocket in orange, hydrogen bonds in green, pi interactions in red)

a) 2D and b) 3D interactions of 8,3ʹ,4ʹ-trihydroxyflavone-7-O-6(6ʺ-O-p-coumaroyl)-β-d-glucopyranoside in the binding site of 6GU7. 3D: Ligand in purple, residues pocket in orange, hydrogen bonds in green, pi interactions in red.

a) 2D and b) 3D interactions of 6,4ʹ-dimethoxy in the binding sites of 5LQF receptor A. 3D: Ligand in purple, residues pocket in orange, hydrogen bonds in green, pi interactions in red.

a) 2D and b) 3D interactions of vicenin-2 isomer 2 in the binding sites of 5LQF receptor D. 3D: Ligand in purple, residues pocket in orange, hydrogen bonds in green, pi interactions in red.

Overlaid 2D interactions diagrams in 6GU7 receptor.
a) Vicenin-2 isomer 2 (green) and the reference inhibitor AZD5438 (red).
b) Vicenin-2 isomer 2 (green) and Dinaciclib (red).

Overlaid 2D interactions diagrams:
a) 6,4ʹ-dimethoxy (green) and the reference inhibitor NU6102 (red) in 5LQF receptor A.
b) Vicenin-2 isomer 2 (green) and Dinaciclib (red) in 5LQF receptor D.

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DOI: https://doi.org/10.2478/eabr-2026-0009 | Journal eISSN: 2956-2090 (formerly 2335-075X, 2956-0454) | Journal ISSN: 2956-0454 (formerly 1820-8665)

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Language: English

Page range: 67 - 78

Submitted on: Sep 16, 2025

Accepted on: Jan 13, 2026

Published on: Jun 1, 2026

Published by: University of Kragujevac, Faculty of Medical Sciences

In partnership with: Paradigm Publishing Services

Keywords:

CDK1,

5LQF,

6GU7,

UDC:

Related subjects:

Clinical medicine, other

© 2026 Ryma Mouna, Abdalwahab Ahmed, published by University of Kragujevac, Faculty of Medical Sciences
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Volume 27 (2026): Issue 1 (March 2026)

In Silico Discovery of Novel CDK1 Inhibitors from Linum Species for Targeted Cancer Therapy

Figures & Tables

Table 1.

Figure 1.

Figure 2.

Table 2.

Table 3.

Table 4.

Table 5.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

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