Synthesis and ABTS Radical,MMP‐1 Inhibitory Activity of CAPE Analogues

In the photoaging process of skin, the ultraviolet (UV)‐induced reactive oxygen species (ROS) is the key regulator of matrix metalloproteinase (MMPs) expression. In this study, a series of Caffeic acid phenethyl ester (CAPE) analogues were synthesized by conjugating the group VI elements (selenium, sulfur, oxygen)‐containing aliphatic alcohols to polyphenolic acids. Their biological activities were evaluated by in vitro testing of their radical scavenging activity the of ABTS [2,2′‐azinobis‐(3‐ethyl‐benzothiazoline‐6‐sulfonic acid)] radical and inhibitory effect against the matrix metalloproteinase‐1 (MMP‐1) activity of collagen degradation and cytotoxicity of a human dermal fibroblast skin cell. Our results suggest these compounds displayed moderate anti‐free radical, potent MMP‐1 inhibitory, and low cytotoxic activities.     

Efficient Total Synthesis of Bongkrekic Acid and Apoptosis Inhibitory Activity of Its Analogues

Bongkrekic acid (BKA), isolated from the bacterium Burkholderia cocovenenans, is an inhibitor of adenine nucleotide translocator, which inhibits apoptosis, and is thus an important tool for the mechanistic investigation of apoptosis. An efficient total synthesis of BKA has been achieved by employing a three‐component convergent strategy based on Kocienski–Julia olefination and Suzuki–Miyaura coupling. It is noteworthy that segment B has been prepared as a new doubly functionalized coupling partner, which contributes to shortening of the number of steps. Torquoselective olefination with an ynolate has also been applied for the efficient construction of an unsaturated ester. Furthermore, it is revealed that 1‐methyl‐2‐azaadamantane N‐oxyl is an excellent reagent for final oxidation to afford BKA in high yield. Based on the total synthesis, several BKA analogues were prepared for structure–activity relationship studies, which indicated that the carboxylic acid moieties were essential for the apoptosis inhibitory activity of BKA. More easily available BKA analogues with potent apoptosis inhibitory activity were also developed.     

Synthesis and Glycosidase Inhibitory Activity of 7‐Deoxycasuarine

Reaction of 1,4‐anhydro‐2,3,5‐tri‐O‐benzyl‐1‐deoxy‐1‐imino‐D ‐arabinitol N‐oxide ( 8 ) with allyl alcohol produced a 3.6 : 1 mixture of the two pyrrolo[1,2‐b]isoxazole derivatives 13 and 14 . The major adduct 13 was converted to 7‐deoxycasuarine ( 7 ), a potent, specific, and competitive inhibitor of amyloglucosidase from Rhizopus mold (see Table).     

Total Synthesis of Indole‐Derived Allocolchicine Analogues Exhibiting Strong Apoptosis‐Inducing Activity

A series of novel pyrrolo‐allocolchicine derivatives (containing a 1‐methyl‐1H‐indol‐5‐yl moiety replacing ring C) was synthesized. The tetracyclic ring system was constructed by Suzuki–Miyaura cross‐coupling of a 1‐methylindole‐5‐boronate with an ortho‐iodo‐dihydrocinnamic acid derivative and subsequent intramolecular Friedel–Crafts acylation. After reduction of the resulting ketone, the nitrogen functionality was introduced in a Mitsunobu‐type reaction by using zinc azide followed by LiAlH₄ reduction. Structural assignments were supported by X‐ray crystallography. The compounds synthesized were then tested against BJAB tumor cells and found to exhibit pronounced cytotoxic activity (proliferation inhibition and apoptosis induction). The ketone 24 b was even active at sub‐nanomolar concentration. In addition, the antitumor potential of the compounds was confirmed by using B lymphoid cell lines.     

Synthesis and Antimicrobial Activity of New Thiazolidine‐Based Heterocycles as Rhodanine Analogues

A new series of compounds containing thiazole nucleus as Rhodanine analogues have been synthesized. The new compounds were prepared from the reactions of the thiosemicarbazones ( 3a,b ) with a series of α‐halo carbonyl compounds to give the corresponding Rhodanine analogues. The thiosemicarbazones derivatives ( 3a,b ) were reacted also with hydrazonoyl chlorides to afford the corresponding tri‐substituted and tetra‐substituted thiazoles. The structures of the newly synthesized compounds were confirmed by elemental analysis and spectral data. The biological activities of the new synthesized Rhodanine analogues' were evaluated for their antimicrobial activities. The results showed that some of these compounds showed excellent activity against two fungal strains, including Aspergillus niger and Aspergillus flavus, in addition to three yeast strains, including Saccharomyces cervesi, Candida albicans NRRL Y‐477, and Candida Pathological specimen compared with the ketoconazol, as the reference drug.     

Design,Synthesis, and Insecticidal Activity of 1,5‐Diphenyl‐1‐pentanone Analogues

Three series of novel 1,5‐diphenyl‐1‐pentanone derivatives were designed and synthesized. Their structures were characterized by IR, ¹H NMR techniques, and elemental analysis. The insecticidal activities of the new compounds were preliminarily evaluated. The bioassay results indicated that the compounds X11 – X30 displayed better aphicidal activity against Aphis gossypii than compounds X1 – X10 and the lead compound (E)‐1,5‐diphenyl‐1‐penten‐1‐one ( A ). The inhibitory rates of compounds X6 and X29 were 100% against Plutella xylostella (L.) at 600 mg·L^?1. Compounds X12 , X13, X19 , X24, X25 , X26 and X27 showed higher insecticidal activity against Tetranychus cinnabarinus (Boisduval) at 600 mg·L^?1 than the lead compound ( A ).     

Synthesis and Inhibitory Activity Evaluation of 2,6‐Disubstituted Purine Derivatives

A series of novel 2,6‐disubstituted purine derivatives were designed and synthesized from 2,6‐dichloropurine. The structures of target compounds were determined by ¹H‐NMR, ¹³C‐NMR, and HRMS. The synthesized compounds were evaluated for their inhibitory activities against lung cancer cell lines of A549 and liver cancer cell lines of Bel‐7402. 2‐(4‐Benzyloxy‐phenylamino)‐6‐(cyclohexylamino)purine( 3 ), 2‐(4‐chloro‐phenylamino)‐6‐(n‐butylamino)purine ( 5 ), 2‐(4‐morpholinoamino)‐6‐(4‐hydroxy‐phenylamino)purine ( 9 ), and 2‐(4‐O‐galactosyl‐phenylamino)‐6‐(cyclohexylamino)purine ( 12 ) exhibited moderate inhibitory activity.     

Synthesis and Antitumor Activity of Tanshinone Analogues

8, 8-Dimethyl-5, 6, 7,8-tetrahydrophenanthrene-3, 4-dione (3) and 8, 8-dimethyl-2- ( 1-hydroxy ethyl) -5,6, 7, 8-tetrahydrophenanthrene-3,4-dione (4), two analogues of the antitumor active tanshinone, were synthesized from anisole. The synthesized compounds 3 and 4 were shown to be highly active against leukemia P-388 cell fine as assayed by in vitro MTT method.     

单螺环哌嗪季铵盐类化合物的合成及镇痛活性研究

为寻找镇痛活性更好的化合物,以前期发现的螺环哌嗪季铵盐类化合物1为先导物,设计合成了8个未见文献报道的衍生物.通过1H NMR,13C NMR和元素分析或高分辨质谱确定了化合物的结构.利用小鼠醋酸扭体模型初步评价了它们的镇痛活性,构效关系研究表明,苯环上的羟基是关键的药效团,与开链季铵盐相比,螺环季铵盐结构对活性更有利;扩大螺环和引入取代基对活性不利.     

Synthesis and Antioxidant Activity of Sapriparaquinone Analogues

It has been considered that the lipid peroxidition damage was involved in aging and pathological disorders. Some phases of atherosclerosis, neuronal ceroid lipofuscinosis, intermittent claudication, oxygen toxicity, and liver injury caused by orotic acid, ethanol, phosphorous or chlorinated hydrocarbons have been discussed in relation to lipid peroxidion1-3. We found that a series of unique 4,5-secoditerpenoidal compounds isolated from the medicinal plant Salvia prionitis showed various bioact…     

双螺环哌嗪季铵盐类化合物的合成及镇痛活性研究

以己二酰氯、哌嗪类化合物和二溴代物为原料,合成了一系列未见文献报道的双螺环哌嗪季铵盐类化合物.通过1HNMR,13CNMR和元素分析确定了化合物的结构.在小鼠醋酸扭体模型上初步评价了它们的镇痛活性,发现多数化合物显示具有较好的镇痛活性,总结出了相应的构效关系.     

Synthesis and Fungicidal Activity of Strobilurin Analogues Containing 1,2,4‐Triazole Oxime Ether Moiety

Strobilurins are a class of important agricultural fungicides that are used widely in plant protection. To find new strobilurin analogues with high activity against resistant pathogens, a series of new strobilurin derivatives bearing 1,2,4‐triazole oxime ether side chain 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h were designed and synthesized. Their structures were confirmed by IR, ¹H NMR, EIMS, and elemental analyses. Bioassays indicated that some of the compounds showed good fungicidal activities in the concentration of 50 mg/L. For example, compound 3f possessed 100%, 100%, and 95.5% inhibition against Fusarium omysporum, Physalospora piricola Nose, and Gibberella saubinetii at the concentration of 50 mg/L, respectively.     

Synthesis and Anticoagulant Activity of Bioisosteric Sulfonic‐Acid Analogues of the Antithrombin‐Binding Pentasaccharide Domain of Heparin

Two pentasaccharide sulfonic acids that were related to the antithrombin‐binding domain of heparin were prepared, in which two or three primary sulfate esters were replaced by sodium‐sulfonatomethyl moieties. The sulfonic‐acid groups were formed on a monosaccharide level and the obtained carbohydrate sulfonic‐acid esters were found to be excellent donors and acceptors in the glycosylation reactions. Throughout the synthesis, the hydroxy groups to be methylated were masked in the form of acetates and the hydroxy groups to be sulfated were masked with benzyl groups. The disulfonic‐acid analogue was prepared in a [2+3] block synthesis by using a trisaccharide disulfonic acid as an acceptor and a glucuronide disaccharide as a donor. For the synthesis of the pentasaccharide trisulfonic acid, a more‐efficient approach, which involved elongation of the trisaccharide acceptor with a non‐oxidized precursor of the glucuronic acid followed by post‐glycosidation oxidation at the tetrasaccharide level and a subsequent [1+4] coupling reaction, was elaborated. In vitro evaluation of the anticoagulant activity of these new sulfonic‐acid derivatives revealed that the disulfonate analogue inhibited the blood‐coagulation‐proteinase factor Xa with outstanding efficacy; however, the introduction of the third sulfonic‐acid moiety resulted in a notable decrease in the anti‐Xa activity. The difference in the biological activity of the disulfonic‐ and trisulfonic‐acid counterparts could be explained by the different conformation of their L ‐iduronic‐acid residues.     

Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity

Our previous study found that desmethylxanthohumol (1) inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol (2) and its dimer analogue rottlerone (3) exhibited more potent α-glucosidase inhibitory activity than 1. The aim of this study was to synthesize a series of rottlerone analogues and evaluate their α-glucosidase and DPP-4 dual inhibitory activity. The results showed that compounds 4d and 5d irreversibly and potently inhibited α-glucosidase (IC₅₀ = 0.22 and 0.12 μM) and moderately inhibited DPP-4 (IC₅₀ = 23.59 and 26.19 μM), respectively. In addition, compounds 4d and 5d significantly promoted glucose consumption, with the activity of 5d at 0.2 μM being comparable to that of metformin at a concentration of 1 mM.