Synthesis, antiproliferative and antimicrobial activities of (KLAKLAK)₂-NH₂ analogue containing nor-Leu and its conjugates with a second pharmacophore

Figures & data

Table 1. Gradient system used for HPLC analysis of target compounds.

Time (min)	Mobile phase А (%)	Mobile phase B (%)
0.01	80	20
10.00	5	95
15.00	5	95
15.50	80	20
22.00	80	20

Table 2. Parameters of MS analysis of target compounds.

Nebulizing gas flow	3 L/min
Heating gas flow	10 L/min
Interface temperature	350 °C
DL temperature	200 °C
Heat block temperature	400 °C
Drying gas flow	10 L/min

Table 3. Structure and analytical data for newly synthesized compounds.

Code	Structure	Molecular formula	ММ exact	[M + H]^+ observed	[M + nNa]^+ observed	tR (min)	M.p. [ C]	${\alpha }_{546}^{20}$ [ ]^a
Si16	(KNleAKNleAK)2-NH2	C71H135N21O15	1522.05	1723.30	1545.25	1.116	123–126	+10
Si17	1,8-NphtG-(KNleAKNleAK)2-NH2	C85H142N22O18	1759.09	1760.30	1782.85	4.567	116–119	−54
Si18	Caf-(KNleAKNleAK)2-NH2	C81H145N21O17	1684.11	–	1729.35	1.122	95–98	−72

^a(c = 1, water).

Figure 1. Antiproliferative activity of newly synthesized compounds. Dose-response curves assessment in (A) breast non-tumorigenic epithelial cells (MCF-10A), (B) mammary gland type A adenocarcinoma (MCF-7) and (C) triple-negative breast cancer (MDA-MB-231).

Table 4. Antiproliferative activity of the studied substances expressed by IC₅₀ values of the mean (± SD).

Code	IC50 of Mean ± SD (μmol/L)
	MCF-10A	MCF-7	MDA-MB-231
Si16	349.7 ± 6.11	321.5 ± 38.12	724.9 ± 4.52
Si17	56.44 ± 2.19	54.1 ± 1.85	161.1 ± 3.33
Si18	128.7 ± 5.35	173.4 ± 7.48	314.7 ± 12.3

Table 5. Antimicrobial activity against microorganisms.

Code	Structures	Zones of inhibition (mm)
		E. coli K12 407	B. subtilis 3562	C. albicans 74
Si16	(KNleAKNleAK)2-NH2	14.66 ± 0.26	13.83 ± 0.21	2.50 ± 0.03
Si17	1,8-NphtG-(KNleAKNleAK)2-NH2	12.66 ± 0.16	14.50 ± 0.26	18.33 ± 0.36
Si18	Caf-(KNleAKNleAK)2-NH2	12.00 ± 0.13	14.16 ± 0.23	5.33 ± 0.07

The experiments were conducted in triplicate for each sample and the diameters of the obtained zones represent the average value of the three results ± SD.

Scheme 1. General steps in the synthesis of the target compounds.