Table 1.

Structures of tacrine, donepezil and rivastigmine derivatives and their biological activities.

S. No.	Structure	Additional Functions	References
1		Antioxidant activity, protective properties against the injury caused by H2O2	[81]
2		2a-d: excellent metal chelating properties. 2a,b: inhibitory potency against AChE-induced Aβ aggregation	[82]
3		Promising in vivo AChE inhibition profile	[83]
4		Inhibitory potency against PAS and AChE-induced Aβ aggregation, ability to induce S-phase post-treatment	[84]
5		Inhibitory potency against Aβ self-aggregation at the level of 47% at 20 µM, antioxidant properties towards PC12 cells from CoCl2-damage	[85]
6		Neuroprotective activity towards SH-SY5Y cells against rotenone plus oligomycin-A or okadaic acid	[86]
7		7b,c,f: neuroprotective activity on SH-SY5Y cell line	[88]
8		Antioxidant properties, inhibition of Aβ1-42 aggregation, neuroprotection of SH-SY5Y in the presence of H2O2	[89]
9		Inhibition of self-/Cu-induced Aβ aggregation, radical scavenging capacity and metal chelating properties (Fe, Cu, Zn), neuroprotection in SH-SY5Y cells treated with Aβ1-42 ascorbate/iron stressors	[96]
10		Inhibition of Aβ self-aggregation amelioration, the impairment of memory in mice models treated with scopolamine in the Morris water maze test	[97]
11		Inhibition of Aβ aggregation	[100]
12		Antioxidant activity and neuroprotection against Aβ1-40 in SH-SY5Y cells	[101]
13		Improvement of cognitive and locomotor activity in a mouse model with AD in the step-through test and open field test, an increase of the amount of H2S in hippocampus, decrease mRNA expression of the proinflammatory cytokines, TNF-α, IL-6, and IL-1β and increase synapse-associated in the hippocampus of tested mice	[108]
14		Inhibition of Aβ42 self-aggregation, neuroprotection in rats neurons in a serum and K+ deprivation model	[111]
15		Ability to cross the BBB in vitro	[120]
16		Inhibition of hMAO A, and MAO-B, strong antioxidant properties	[127]
17		Strong antioxidant effect with the oxygen radical absorbance capacity	[129]
18		Inhibition of MAO-B and Aβ1−42 aggregation, antioxidant effect, ability to chelat Cu2+ ions, to protect PC12 cells from oxidative stress caused by H2O2, rotenone, and oligomycin-A, to protect BV-2 cells from LPS-Stimulated Inflammation, improvement of cognition and spatial memory against scopolamine-induced acute memory deficit, D-galactose (D-gal) and AlCl3 induced chronic oxidative stress in mice model without acute toxicity and hepatotoxicity, ability to cross the BBB in vitro	[130]
19		Inhibitory activity against hMAO-B, self-induced and hAChE-induced Aβ aggregation, antioxidant properties, the neuroprotective effects on PC12 cells treated with H2O2 and against LPS-stimulated inflammation on BV-2 cells, ability to cross the BBB in vitro, good liver metabolic stability in RLM, dose-dependently reversed scopolamine-induced memory deficit in mice model but without acute toxicity	[131]
20		Anti-inflammatory properties in vivo in mice model, antioxidant activity in SH-SY5Y cell line and ability to chelate Cu2+ and Fe2+ ions, protection of SH-SY5Y cells against the late neuronal death caused by Aβ1-42 oligomers	[132]
21		ADME profile in silico, anti-inflammatory and neuroprotective activity against AβO-induced neuroinflammation and neurodegeneration in vitro in THP-1 cells and in vivo in mice model	[135]
22		Inhibitory activity against BACE1 and Aβ1−42 aggregation, neuroprotective properties against Aβ1−42-induced damage in SH-SY5Y cells	[139]
23		Inhibitory activity against Aβ self-aggregation and Cu2+-induced Aβ aggregation, ability to protect SH-SY5Y cells from the Aβ-induced toxicity	[141]
24		Inhibitory potency against MAO-B, ability to cross the BBB in vitro	[143]
25		Selective Cu2+ chelator in a 1:1 ratio, ability to cross the BBB in vitro, activity against MAO-B	[144]
26		Inhibition of PDE9A	[153]
27		Ability to inhibit self-induced and Cu2+-induced Aβ1-42 aggregation, inhibitory activity against MAO-B, antioxidative properties, ability to chelate metals and to cross the BBB in vitro	[154]
28		Prevention from ROS in SH-SY5Y cell line	[155]
29		Anti-inflammatory and antioxidant activity in BV-2 cells, the induction of proteins expression (i.e. GSH) involved in the antioxidant defense in SH-SY5Y cell line, a decrease of ROS levels and NO-release in BV-2 cells	[156]
30		Antioxidative activity, selective metal chelator and neuroprotector against H2O2-induced PC12 cell injury, ability to pass the BBB in vitro, relevant neuroprotective effects in scopolamine-induced cognitive impairment in mice model	[157]
31		31a-c: pleiotropic activities 31d-f: protection from the self-mediated Aβ aggregation, 31e,f: neuroprotective effect in HT22 cells against glutamate-índuced neuronal death	[158]
32		Prevention of Aβ self-aggregation in TEM observation, ABTS+ scavenging, and ability to chelat Cu2+ ions	[159]
33		Prevention of Aβ self-aggregation, protection of HT22 cells from glutamate and H2O2 induced cell death, scavenging free radicals and Cu2 ions chelation	[160]
34		Antioxidant activity, neuroprotection of H2O2- induced PC12 cells and Aβ1-42- induced SH-SY5Y cells, hepatoprotection of H2O2- induced LO2 cells, selective metal chelator, activity against Cu2+/hAChE/self-induced Aβ1-42 aggregation, disaggregation of Cu2+-induced Aβ1-42 aggregation, ability to pass the BBB in vitro	[161]