Compounds with 1,3,4-oxadiazole and azinane appendages to evaluate enzymes inhibition applications supported by docking and BSA binding

Figures & data

Table 1. Different substituents of aralkyl/phenyl/aryl group

Comp	R	Comp	R	Comp	R
6a		6g		6l
6b		6h		6m
6c		6i		6n
6d		6j		6o
6e		6k		6p
6f

Table 2. AChE inhibition studies

Compounds	AChE
	% at 0.5 mM	IC50 μmoles
6a	85.36 ± 0.16	62.54 ± 0.12
6b	58.74 ± 0.24	418.37 ± 0.17
6c	12.43 ± 0.13	–
6d	61.92 ± 0.21	412.89 ± 0.18
6e	59.54 ± 0.22	412.93 ± 0.17
6f	31.25 ± 0.15	–
6g	61.64 ± 0.17	335.82 ± 0.14
6h	42.52 ± 0.21	–
6i	57.23 ± 0.26	451.29 ± 0.19
6j	67.34 ± 0.19	168.73 ± 0.15
6k	88.72 ± 0.16	47.69 ± 0.13
6l	49.16 ± 0.17	–
6m	65.38 ± 0.21	134.85 ± 0.15
6n	59.65 ± 0.23	389.57 ± 0.18
6o	68.23 ± 0.19	155.36 ± 0.16
6p	89.75 ± 0.18	28.54 ± 0.13
Eserine	91.27 ± 1.17	0.04 ± 0.0001

Table 3. Anti-urease activity

Compound	Urease inhibition
	Inhibition (%) at 0.125 mM	IC50 (μM)
6a	97.93 ± 0.03	1.12 ± 0.004
6b	97.72 ± 0.04	2.21 ± 0.003
6c	97.41 ± 0.02	1.13 ± 0.004
6d	97.62 ± 0.06	2.16 ± 0.002
6e	97.82 ± 0.01	1.24 ± 0.002
6f	97.64 ± 0.02	1.27 ± 0.005
6g	97.51 ± 0.05	1.21 ± 0.006
6h	97.46 ± 0.03	1.13 ± 0.002
6i	97.12 ± 0.06	1.15 ± 0.004
6j	97.34 ± 0.06	1.23 ± 0.002
6k	97.53 ± 0.07	2.11 ± 0.006
6l	97.18 ± 0.03	2.14 ± 0.002
6m	97.72 ± 0.04	1.12 ± 0.003
6n	97.27 ± 0.06	1.32 ± 0.003
6o	97.46 ± 0.02	6.21 ± 0.005
6p	97.15 ± 0.04	1.43 ± 0.002
Thiourea	96.24 ± 0.16	21.36 ± 0.14

Note: Data is mean of three values (mean ± s.e.m., n = 3).

Figure 1. Obtained binding modes of ligands in the main binding site of Acetylcholinesterase. (A) Superimposing of compounds 6p (Purple), 6a (Green) and 6e (Yellow) docked to AChE. (B) Binding mode of compound 6p in AChE main binding site. (C) Binding mode of compound 6e in AChE main binding site. (D) Binding mode of compound 6a in AChE main binding site.

Table 4. Binding constant and number of binding site of compounds warfarin and ibuprofen with BSA at 298 K

Compounds	Ksv (L/mol) × 10^4	Kq (L/mols^−1) × 10^12	Ka (L/mol)	N
6a	15.5676	15.5676	3.23 × 10^7	1.56
6k	6.4373	6.4373	1.05 × 10^4	0.81
6l	2.5462	2.5462	4.12 × 10^4	1.05
6p	12.3306	12.3306	8.49 × 10^4	0.98
6m	4.2493	4.2493	1.62 × 10^5	1.13

Figure 2. Fluorescence spectra of BSA in presence of different amounts of selected compounds (6k, 6l, 6m, and 6p) at 295 nm and 298 K (inset graph corresponding to the Stern-Volmer plot).

Scheme 1. General scheme for the synthesis of 2-(5-(1-(4-nitrophenylsulfonyl)piperidin-4-yl)-1,3,4-oxadiazol-2-ylthio)-N-(substituted)acetamide (6a–p). (A) 15% Na₂CO₃ solution, H₂O, stir for 8 h. (B) N₂H₄.H₂O, EtOH, reflux for 5 h. (C) KOH (s), EtOH, reflux for 6 h. (D) BrCH₂COBr, 15% Na₂CO₃ solution, H₂O, stir for 2 h. (E) DMF, NaH, stir for 24 h.