1. Synthesis and structural characterization of fluorinated thiosemicarbazones
Juan L Bautista, Marcos Flores-Alamo, Jorge Tiburcio, Rebeca Vieto, Hugo Torrens Molecules. 2013 Oct 22;18(10):13111-23. doi: 10.3390/molecules181013111.
Six new fluorinated thiosemicarbazones R‑C(R')=N-NH-C(S)NH(2) (R = 2,4-C(6)H(3)F(2), R' = H (1); R = 2,5-C(6)H(3)F(2), R' = H (2); R = 2,6-C(6)H(3)F(2), R' = H (3); R = 3,4-C(6)H(3)F(2), R' = H (4); R = 3,5-C(6)H(3)F(2), R' = H (5) and R = 4-C(6)H(4)F, R' = C(6)H(5), (6)) have been prepared. The molecular structures of compounds 1 to 6 have been determined.
2. Dual l-Carnosine/ Aloe vera Nanophytosomes with Synergistically Enhanced Protective Effects against Methylglyoxal-Induced Angiogenesis Impairment
Behrad Darvishi, Rassoul Dinarvand, Hadiseh Mohammadpour, Tunku Kamarul, Ali Mohammad Sharifi Mol Pharm. 2021 Sep 6;18(9):3302-3325. doi: 10.1021/acs.molpharmaceut.1c00248. Epub 2021 Jul 23.
Microvascular complications are among the major outcomes of patients with type II diabetes mellitus, which are the consequences of impaired physiological functioning of small blood vessels and angiogenic responses in these patients. Overproduction and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl byproduct of glycolysis pathway, has been acclaimed as the main inducer of impaired angiogenic responses and microvascular dysfunction in diabetic patients with uncontrolled hyperglycemia. Hence, an effective approach to overcome diabetes-associated microvascular complications is to neutralize the deleterious activity of enhanced the concentration of MGO in the body. Owing to the glycation inhibitory activity of Aloe vera whole extract, and capability of l-carnosine, an endogenous dipeptide, in attenuating MGO's destructive activity, we examined whether application of a combination of l-carnosine and A. vera could be an effective way of synergistically weakening this reactive dicarbonyl's impaired angiogenic effects. Additionally, overcoming the poor cellular uptake and internalization of l-carnosine and A. vera, a nanophytosomal formulation of the physical mixture of two compounds was also established. Although l-carnosine and A. vera at whole studied combination ratios could synergistically enhance viability of human umbilical vein endothelial cells (HUVECs) treated with MGO, the 25:1 w/w ratio was the most effective one among the others (27 ± 0.5% compared to 12 ± 0.3 to 18 ± 0.4%; F (4, 15) = 183.9, P < 0.0001). Developing dual nanophytosomes of l-carnosine/A. vera (25:1) combination ratio, we demonstrated superiority of the nanophytosomal formulation in protecting HUVECs against MGO-induced toxicity following a 24-72 h incubation period (17.3, 15.8, and 12.4% respectively). Moreover, 500 μg/mL concentration of dual l-carnosine/A. vera nanophytosomes exhibited a superior free radical scavenging potency (63 ± 4 RFU vs 83 ± 5 RFU; F (5, 12) = 54.81, P < 0.0001) and nitric oxide synthesizing capacity (26.11 ± 0.19 vs 5.1 ± 0.33; F (5, 12) = 2537, P < 0.0001) compared to their physical combination counterpart. Similarly, 500 μg/mL dual l-carnosine/A. vera nanophytosome-treated HUVECs demonstrated a superior tube formation capacity (15 ± 3 vs 2 ± 0.3; F (5, 12) = 30.87, P < 0.001), wound scratch healing capability (4.92 ± 0.3 vs 3.07 ± 0.3 mm/h; F (5, 12) = 39.21, P < 0.0001), and transwell migration (586 ± 32 vs 394 ± 18; F (5, 12) = 231.8, P < 0.001) and invasion (172 ± 9 vs 115 ± 5; F (5, 12) = 581.1, P < 0.0001) activities compared to the physical combination treated ones. Further confirming the proangiogenic activity of the dual l-carnosine/A. vera nanophytosomes, a significant shift toward expression of proangiogenic genes including HIF-1α, VEGFA, bFGF, KDR, and Ang II was reported in treated HUVECs. Overall, dual l-carnosine/A. vera nanophytosomes could be a potential candidate for attenuating type II DM-associated microvascular complications with an impaired angiogenesis background.
3. Linear Nonalternant Isomers of Acenes Fusing Multiple Azulene Units
Shangshang Wang, Min Tang, Lin Wu, Lifang Bian, Liang Jiang, Jiali Liu, Zheng-Bin Tang, Yimin Liang, Zhichang Liu Angew Chem Int Ed Engl. 2022 Aug 15;61(33):e202205658. doi: 10.1002/anie.202205658. Epub 2022 Jul 8.
A modular approach to azulene building blocks was developed starting from readily available aryl-substituted cyclopentadiene and ortho-haloaryl aldehyde by dehydration condensation followed by palladium-catalyzed C-H coupling. It facilitates the synthesis of four nonalternant isomers of pentacene and hexacene, namely, dibenzo[e,g]azulene, benzo[1,2-f : 5,4-f']diazulene, benzo[1,2-f : 4,5-f']diazulene, and naphtho[2,3-f : 6,7-f']diazulene, which exhibit narrow band gaps with high stability in addition to protonation-caused enhanced near-infrared fluorescence. We discovered that in these isomers, i) constitutional isomerism influences significantly their photoelectric properties and ii) the elongation of the conjugation system does not necessarily lead to a narrowing in the band gap. Due to the easy modifiability of the nonazulene building blocks, this strategy can be extended to modularly prepare numerous multiazulene-fused aromatics.
