Novel derivatives of Costus igneus towards potentiality against diabetes mellitus receptors: ADME/Tox profiling, Computational Docking, and Molecular Dynamics Simulation study

Figures & data

Figure 1. Costus igneus plant.

Figure 2. Therapeutic targets for diabetes mellitus and their underlying mechanisms: (a) IR, (b) DPP-IV, and (c) PPAR-γ.

Table 1. Phytoconstituents’ dossier of physiochemical characteristics.

S.No.	Phytochemicals	PubChem ID	Molecular structure	2-D structure	ADMET Analysis
1.	Corosolic acid	6918774	C30H48O4		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	472.7 3 4 4.97 1 High No No 2000
2.	Diosgenin	99474	C27H42O3		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	414.62 1 3 4.94 1 High Yes No 8000
3.	β-sitosterol	222284	C29H50O		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	414.71 1 1 6.73 1 Low No No 890
4.	Quercetin	5280343	C15H10O7		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	302.24 5 7 −0.56 0 High No No 159
5.	Catechin	9064	C15H14O6		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	290.27 5 6 0.24 0 High No No 10000
6.	Roseoside	9930064	C19H30O8		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	386.44 5 8 −1.06 0 Low No No 1750
7.	Epicatechin	72276	C15H14O6		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	290.27 5 6 0.24 0 High No No 10000
8.	Kaempferol	5280863	C15H10O6		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	286.24 4 6 −0.03 0 High No No 3919
9.	Christinin– – A	101324802	C19H24O7		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	406.47 0 7 2.34 0 High No No 7
10.	β-amyrin	73145	C30H50O		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	410.72 0 0 8.91 1 Low No No 5000
11.	Hexadecanoic acid	985	C16H32O2		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	256.42 1 2 4.19 1 High Yes No 900
12.	Epigallocatechin gallate	65064	C22H18O11		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	458.37 8 11 −0.44 2 Low No No 1000
13.	Stigmasterol	5280794	C29H48O		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	412.69 1 1 6.62 1 Low No No 890
14.	Tetradecanoic acid	11005	C14H28O2		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	228.37 1 2 3.69 0 High Yes No 900
15.	Oleic acid	445639	C18H34O2		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	282.46 1 2 4.57 1 High No No 48
16.	Squalene	638072	C30H50		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	410.72 0 0 7.93 1 Low No No 5000
17.	Lupeol	259846	C30H50O		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	426.72 1 1 6.92 1 Low No No 2000
18.	β-carotene	5280489	C40H56		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	536.87 0 0 8.96 2 Low No No 1510
19.	Glycyrrhetinic acid	10114	C30H46O4		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	470.68 2 4 4.87 1 High No No 560
20.	α-tocopherol	14985	C29H50O2		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	430.71 1 2 6.14 1 Low No No 5000
21.	Farnesyl acetone	1711945	C18H30O		Molecular weight H bond donor H bond acceptor Lipophilicity Violations HIA BBB Carcinogen LD50(mg/kg)	262.43 0 1 4.5 1 High No No 5000

Figure 3. Human therapeutic target X-ray conformations of diabetes mellitus receptors. (a) IR (b) DPP-IV (c) PPAR-γ.

Figure 4. Graphical depiction of the binding energy of phytoconstituents against Diabetes mellitus targeted therapies highlighting foremost docked compounds similar to their reference counterpart (a) IR (b) DPP-IV (c) PPAR-γ.

Table 2. The binding energy of phytoconstituents selected for docking towards diabetes mellitus targeted therapies.

Selected Phytoconstituents	IR	DPP-IV	PPAR-γ
Corosolic acid	−8.18	−4.78	−2.42
Diosgenin	−8.85	−5.51	−8.01
β-sitosterol	−8.81	−8.72	−12.29
Quercetin	−7.51	−6.46	−7.76
Catechin	−7.29	−6.66	−7.93
Roseoside	−7.25	−6.38	−8.09
Epicatechin	−7.09	−6.11	−8.22
Kaempferol	−7.49	−6.38	−7.50
Christinin– – A	−7.84	−6.48	−9.02
β-amyrin	−8.55	−7.59	−4.97
Hexadecanoic acid	−3.70	−3.24	−6.13
Stigmasterol	−8.92	−8.18	−11.81
Tetradecanoic acid	−3.36	−3.29	−5.98
Oleic acid	−3.96	−3.94	−7.08
Squalene	−6.38	−6.03	−9.84
Lupeol	−8.62	−6.73	−8.92
Glycyrrhetinic acid	−8.09	−8.74	−4.06
α– – tocopherol	−7.44	−6.42	−11.39
Farnesyl acetone	−6.00	−5.96	−8.34
Reference	−5.70	−8.60	−9.68

Figure 5. 3D and 2D illustrations of foremost docked complexes (A) IR (B) DPP-IV (C)PPAR-γ

Figure 6. 2D depiction of the best-fitting ligand and reference with their corresponding receptors (a) IR (b) DPP-IV (c) PPAR-γ.

Figure 7. RMSD and RMSF plot of (a) Stigmasterol with IR (b) Glycyrrhetinic acid with DPP-IV (c) β-sitosterol with PPAR-γ.

Figure 8. Ligand torsion profile of (a) Stigmasterol with IR (b) Glycyrrhetinic acid with DPP-IV (c) β-sitosterol with PPAR-γ.

Figure 9. Protein–Ligand contact histogram and timeline representation (a) Stigmasterol–IR complex (b) Glycyrrhetinic acid–DPP-IV (c) β-sitosterol–PPAR-γ.

Table 3. Protein secondary structure elements (SSE) interpretation.

Selected Ligands	% α-helix	% β-strand	% Total SSE
Stigmasterol	24.66	14.5	39.16
Glycyrrhetinic acid	11.26	32.38	43.64
β-sitosterol	51.26	3.54	54.8