The synthesis of some β-lactams and investigation of their metal-chelating activity, carbonic anhydrase and acetylcholinesterase inhibition profiles

Figures & data

Scheme 1. The synthesis route of β-lactam derivatives.

Table 1. The synthesis of imine derivatives (10–14).

Table 2. The addition reactions of imines and dichloroketene compounds.

Figure 1. Standard compounds used for carbonic anhydrase I and II isoenzymes (acetazolamide and dorzolamide) and acetylcholinesterase (tacrine) inhibitors.

Table 3. The enzyme inhibition values of some imines (10–14) and β-lactam analogs (15–19) against human carbonic anhydrase isoenzymes I and II (hCA I and II) and acetylcholinesterase (AChE) enzyme.

	IC50 (nM)						KI (nM)
Compounds	hCA I	r^2	hCA II	r^2	AChE	r^2	hCA I	hCA II	AChE
10	7.79	0.9816	10.21	0.9516	3.21	0.9695	5.31 ± 0.39	7.27 ± 0.91	1.57 ± 0.55
11	6.30	0.9829	7.79	0.9611	2.76	0.9933	4.67 ± 0.54	9.93 ± 4.19	1.48 ± 0.06
12	6.93	0.9646	8.66	0.9655	3.01	0.9714	9.09 ± 4.06	8.98 ± 1.80	1.01 ± 0.46
13	8.25	0.9783	9.12	0.9644	2.44	0.9776	7.45 ± 1.42	10.29 ± 3.55	0.82 ± 0.34
14	10.83	0.9727	14.74	0.9339	3.03	0.9434	11.18 ± 1.98	10.41 ± 2.69	1.36 ± 0.54
15	4.59	0.9688	7.37	0.9561	1.35	0.9632	4.81 ± 1.78	6.59 ± 2.51	0.82 ± 0.39
16	3.59	0.9911	5.29	0.9709	1.18	0.9760	3.22 ± 0.22	3.74 ± 0.39	0.50 ± 0.20
17	4.15	0.9856	5.02	0.9606	1.39	0.9631	3.40 ± 0.82	4.37 ± 1.74	0.89 ± 0.37
18	5.09	0.9831	6.13	0.9616	1.52	0.9496	3.74 ± 0.71	5.88 ± 2.32	0.61 ± 0.15
19	7.37	0.9727	7.88	0.9382	1.97	0.9593	4.99 ± 0.69	7.08 ± 1.46	0.94 ± 0.35
AZA*	101.19	0.9509	113.75	0.9791	–	–	170.34 ± 2.48	115.43 ± 1.63	–
DZA*	88.45	0.9760	93.01	0.9910	–	–	129.26 ± 0.21	135.67 ± 0.32	–
TAC**	–	–	–	–	9.76	0.9463	–	–	5.70 ± 1.09

*Acetazolamide (AZA) and dorzolamide (DZA) were used as a standard inhibitor for all hCA I and II.

**Tacrine (TAC) was used as a standard inhibitor for AChE enzyme.

Table 4. Determination of half maximal concentrations (IC₅₀, μg/mL) of Fe²⁺ chelating of some imines (10–14) and β-lactam analogs (15–19) and standard compounds.

Compounds	Fe^2+ chelating	r^2
BHA	36.47	0.9837
BHT	57.75	0.9922
α-Tocopherol	18.73	0.9861
Trolox	28.88	0.9828
EDTA	12.83	0.9924
10	76.15	0.9855
11	113.60	0.9944
12	85.56	0.9813
13	49.50	0.9737
14	57.75	0.9983
15	138.60	0.9889
16	230.01	0.9783
17	98.89	0.9828
18	77.01	0.9911
19	115.50	0.9728