Synthesis and Biological Activity of Mustard Derivatives of Thymine

The synthesis and biological activity of a novel DNA cross-linking antitumor agent is presented. The new alkylating agent significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line.     

Synthesis and Biological Activity of Fatty Acid Derivatives of Quinine

Derivatives of quinine with fatty acids including polyunsaturated fatty acids were prepared. They showed moderate antimalarial activity as compared with quinine itself using Plasmodium falciparum. The activities were not dependent on whether the fatty acyl group was saturated or unsaturated. On the other hand, the derivatives showed significantly higher cytotoxicity against a mammary tumor cell line FM3A than quinine itself. Calculating from these data, an acetyl derivative of quinine with the shortest acyl group was found to give the highest selectivity.     

Design,Synthesis, and Biological Activity of Guaiazulene Derivatives

Guaiazulene and related derivatives were famous for diverse biological activities. In an effort to discover new highly efficient candidate drugs derived from guaiazulene, four series of guaiazulene derivatives were designed, synthesized, and evaluated for antiproliferation, antiviral, anti-inflammatory and peroxisome proliferators-activated receptor γ (PPARγ) signalling pathway agonist activities. Among them, two guaiazulene condensation derivatives showed selective cytotoxic activities towards K562 cell with IC₅₀ values 5.21 μM and 5.14 μM, respectively, accompanied by slight effects on normal cell viability. For the first time, one guaiazulene derivative from series I exhibited potent antiviral activity towards influenza A virus with IC₅₀ of 17.5 μM. A guaiazulene-based chalcone showed higher anti-inflammatory activity than positive drug indomethacin with an inhibitory rate of 34.29 % in zebrafish model in vivo. One guaiazulene-based flavonoid could strongly agitate PPARγ pathway at 20 μM, indicating the potential of guaiazulene derivatives to reduce obesity development and ameliorate hepatic steatosis. Preliminary in silico ADME studies predicted the excellent drug-likeness properties of bioactive guaiazulene derivatives.     

Synthesis,Biological Activity and Action Mechanism Study of Novel Chalcone Derivatives Containing Malonate

A series of novel chalcone malonate derivatives were synthesized and their antibacterial and antiviral activities were evaluated. All target compounds were characterized by spectral data. The results of antimicrobial bioassay showed that one compound (diethyl [3‐(naphthalen‐2‐yl)‐1‐(3‐nitrophenyl)‐3‐oxopropyl]propanedioate) showed excellent antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), with an EC₅₀ value of 10.2 μg/mL, which is significantly superior to bismerthiazol (71.7 μg/mL) and thiodiazole copper (97.8 μg/mL). At the same time, the mechanism of two compounds was confirmed by scanning electron microscopy. In addition, another compound (diethyl [3‐(naphthalen‐2‐yl)‐1‐(4‐nitrophenyl)‐3‐oxopropyl]propanedioate) showed significant curative activity to tobacco mosaic virus, with a value of 74.3 %, which was superior to 53.3 % of ningnanmycin. The results of microscale thermophoresis also showed that the Kd value of the combination of two compounds with the coat protein of tobacco mosaic virus was 0.211 and 0.166 μmol/L, which was better than 0.596 μmol/L of ningnanmycin. At the same time, the molecular docking of two compounds with tobacco mosaic virus‐coat protein shows that the compound is well embedded in the pocket between the two subunits of tobacco mosaic virus‐coat protein. These results show that chalcone derivatives containing malonate group can be considered as activators in the design of antibacterial and antiviral agents.     

Synthesis of Lipid Derivatives of Pyrrole Polyamide and Their Biological Activity

Novel fatty acyl and phospholipid derivatives of pyrrole polyamide were synthesized. Their cytotoxicity against a cancer cell line of MT-4 cells and those infected by human immunodeficiency virus (HIV) was examined. Although no anti-HIV activity was found, their cytotoxicitty against the cancer cells was significantly enhanced by introducing a lipophilic group into the pyrrole polyamide.     

靛红衍生物的合成及其对稻瘟菌的生物活性

以靛红为原料合成了系列3-亚胺基/亚甲基-吲哚-2-酮化合物及其Mannich碱衍生物,研究了它们在抗稻瘟菌方面的活性,发现了这两种类型的若干化合物有较好的抑制稻瘟菌孢子萌发的活性,初步讨论了构效关系。认为1位的羟甲基和胺甲基、3位的亚甲基是药效团,芳基亚甲基苯环上对位取代基、羟基取代基和吸电子取代基不利于活性的提高,邻位的供电子取代基有利于活性的提高。     

Synthesis and Biological Activity of Urea and Thiourea Derivatives from 2-Aminoheterocyclic Compounds

Thirty-eight N-substituted-N′-(2-thiozolyl and furfuryl)ureas and thioureas were prepared by reaction of 2-aminothiazole and 2-furfurylamine with the appropriate iso(thio)cyanate. All compounds were tested for herbicidal activity and selectivity on seedlings of wheat (a monocotyledonous plant) and cucumber (a dicotyledonous plant). Only one compound (1) out of 14 ureas was characterized by considerable herbicidal activity against the wheat seedlings and two compounds (1 and2)-towards the cucumber seedlings. The phenylurea derivative of 2-aminothiazole (1) was 1.7-fold more and the 3-chlorophenylurea derivative of 2-furfurylamine (23) was equally as active as the standard diuron with respect to selective herbicidal activity. Among 24 thioureas, four compounds (15, 16, 17, and18) to displayed the highest selective herbicidal activity and two other compounds (19 and33) were almost equal to diuron activity. Selective herbicidal ratio (SHR) represents the degree of herbicidal effect of the investigated compounds compared to diuron at both test objects. Four compounds (16,17,18, and23) possessed SHR ≪100 in the wheat seedlings while in the cucumber seedlings they had SHR ≫ 100. Therefore these compounds were substantially more active herbicides to the wheat seedlings as compared to diuron. The cytokinin-like activity of the synthesized compounds was also investigated in terms of betacyanin synthesis and radish cotyledon enlargement. The urea derivatives exhibited mostly high cytokinin-like activity but their activity remained lower than those of kinetin and N-phenyl-N′-(4-pyridyl)urea. The N-(3-fluorophenyl)-N′-(2-thiazolyl)urea (2) possessed the greatest activity at 10 μM while the corresponding compound with 3-chlorophenyl (4) was the most active cytokinin-like substance in the whole concentration range tested. Attention was also given to structure-activity relationships for the screened compounds. In general, the ureas and thioureas containing a 2-thiazole ring were more active than those containing a 2-furfuryl residue. Online publication: 7 April 2005     

Synthesis and Biological Activity of Some Bromophenols and Their Derivatives Including Natural Products

In addition to the first synthesis of the natural bromophenol butyl 2-(3,5-dibromo-4-hydroxyphenyl)acetate ( 1 ), indene derivatives 34 and 35 were synthesized from 3-phenylpropenal derivatives in BBr₃ medium. Five known natural bromophenols and some derivatives were synthesized by known methods. Cholinesterase (ChEs) inhibitors reduce the breakdown of acetylcholine and are used in the treatment of Alzheimer's disease (AD) and dementia symptoms. The inhibition effects of all obtained compounds were examined towards acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glycosidase enzymes. All synthesized compounds demonstrated the strong inhibition effects against both cholinergic enzymes. For determination of Ki values of novel bromophenols Lineweaver-Burk graphs were obtained. Ki values were found in the ranging of 0.13–14.74 nM for AChE, 5.11–23.95 nM for BChE, and 63.96–206.78 nM for α-glycosidase, respectively. All bromophenols and their derivatives exhibit effective inhibition profile when compared to positive controls.     

Synthesis and Biological Activity of the Lipophilic Derivatives of N- Acetyl-1-thiomuramoyl-l-alanyl-d-isoglutamine

A variety of the lipophilic derivatives at C-1 and C-6 in N-[2-O-(2-acetamido-2,3-dideoxy-1-thio-β-d-glucopyranose-B-yl)-d-lactoy]-l-alanyl-(N¹-fatty acyl)-d-isoglutamine methyl esters were synthesized from 2N-acetyl-1-S-acetyl-4,6-O-isopropylidene-1-thiomuramoyl-l-alanyl-d-isogluta-mine methyl ester. Their immunoadjuvant activity in guinea-pigs, and the protective effect in mice infected with Escherichia coli (E-77156) were examined.     

Synthesis and Biological Activity of Nitrilic Derivatives of the Methyl Ester of Maleopimaric Acid

An effective method of a modification of the anhydride ring of the maleopimaric acid methyl ester by means of the cyanoethylation reaction was developed. A primary screening of a cytotoxic activity in vitro demonstrated an ability of the cyanoethyl derivative of the maleopimaric acid methyl ester to induce the death of the PC-3 cells of prostate cancer.     

Synthesis,Biological Activity Evaluation and Molecular Docking of Imidazole Derivatives Possessing Hydrazone Moiety

In an attempt to identify potential active anticancer agents with low cytotoxic properties and CA inhibitors, a new series of hybrid compounds incorporating imidazole ring and hydrazone moiety as part of their structure were synthesized by aza-Michael addition reaction followed by intramolecular cyclization. The structure of synthesized compounds was elucidated using various spectral techniques. Synthesized compounds were evaluated for their in vitro anticancer (prostate cell lines; PC3) and CA inhibitory (hCA I and hCA II) activity. Among them, some compound displayed remarkable anticancer activity and CA inhibitory activity with K_i values in range of 17.53±7.19–150.50±68.87 nM against cytosolic hCA I isoform associated with epilepsy, and 28.82±14.26–153.27±55.80 nM against dominant cytosolic hCA II isoforms associated with glaucoma. Furthermore, the theoretical parameters of the bioactive molecules were calculated to establish their drug-likeness qualities. The proteins used for the calculations are prostate cancer protein (PDB ID: 3RUK and 6XXP). ADME/T analysis was carried out to examine the drug properties of the studied molecules.     

Synthesis and Biological Activities of Phosphonylalkylpurine Derivatives

Abstract

Syntheses and biological activities of 2-phosphonylmethoxy-ethyl (PME) purine analogs are described.     

Synthesis and Biological Activity of New 4‐tert‐Butylcyclohexanone Derivatives

In the synthesis performed in this study, derivatives of 4‐tert‐butylcyclohexanone 1 were obtained using typical reactions of organic synthesis. The bioactivity of the selected compounds was evaluated. 1‐(Bromomethyl)‐8‐tert‐butyl‐2‐oxaspiro[4.5]decan‐3‐one ( 5 ) was characterized by attractant properties against larvae and a weak feeding deterrent activity against adults of Alphitobius diaperinus Panzer . This bromolactone was a moderate antifeedant towards Myzus persicae Sulzer . In addition, ethyl (4‐tert‐butylcyclohexylidene)acetate ( 2 ) and bromolactone 5 displayed antibacterial activity. The strongest bacteriostatic effect was observed against Gram‐positive strains: Bacillus subtilis and Staphylococcus aureus. The bromolactone 5 also limited the growth of Escherichia coli strain.     

Design,Synthesis, Biological Activity Evaluation and Action Mechanism of Myricetin Derivatives Containing Thiazolebisamide

The plant diseases caused by a variety of pathogens such as viruses, bacteria and fungi pose a great threat to global food production and food safety. Therefore, the search for green, efficient and pollution-free pesticides has become an important task. In this article, 23 myricetin derivatives containing thiazolebisamides active groups have been designed and synthesized. Their activities were evaluated by performing in vitro antibacterial and in vivo antiviral assays, microscale thermophoresis (MST) and molecular docking assays. The results of in vivo antiviral assays showed that compounds A4 and A23 exhibited good antiviral activity with EC₅₀ values of 79.0 and 54.1 μg/mL for therapeutic activity and 103.3 and 91.2 μg/mL for protective activity, respectively. The dissociation constants (Kd) values of compounds A4 and A23 against TMV-CP were 0.021 and 0.018 μM, respectively, determined by microscale thermophoresis (MST), which were much smaller than those of the commercial drug ningnanmycin (NNM), which were 2.84 μM. The interaction of compounds A4 , A23 with TMV-CP was further verified at the molecular level. In addition, in vitro antifungal assays of this series of compounds showed that they exhibited some inhibitory activity against a variety of fungi, especially against the phytophthora capsici. Among them, A13 and A20 showed similar inhibitory activity to the control drug azoxystrobin at 100 μg/mL against the phytophthora capsici.     

朱砂七粗多糖的提取及生物活性的研究

首次从朱砂七中提取粗多糖(PCCP),研究了PCCP对.OH自由基、O2-.自由基和DPPH.自由基的清除能力以及抗脂质过氧化能力,选用人肝癌细胞HepG2,经MTT染色法研究其体外抗肿瘤活性。结果显示,PC-CP的浓度在8.48 mg/mL时,对.OH、O2-.和DPPH.的清除率分别达到了52.3%、54.7%和38.3%;PCCP的浓度在8.48 mg/mL时,对脂质过氧化的抑制率达到了62.0%;PCCP的浓度在277.78μg/mL时,对人肝癌细胞HepG2的抑制率达到了42.6%,表明PCCP具有一定的体外抗氧化能力和体外抗肿瘤活性。     

Biological Activity of Novel Synthetic Derivatives of Carnosine

Two novel derivatives of carnosine—(S)-trolox-l-carnosine (STC) and (R)-trolox-l-carnosine (RTC) are characterized in terms of their antioxidant and membrane-stabilizing activities as well as their resistance to serum carnosinase. STC and RTC were synthesized by N-acylation of l-carnosine with (S)- and (R)-trolox, respectively. STC and RTC were found to react more efficiently with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and protect serum lipoproteins from Fe²⁺-induced oxidation more successfully than carnosine and trolox. At the same time, STC, RTC and trolox suppressed oxidative hemolysis of red blood cells (RBC) less efficiently than carnosine taken in the same concentration. When oxidative stress was induced in suspension of cerebellum granule cells by their incubation with N-methyl-d-aspartate (NMDA), or hydrogen peroxide (H₂O₂), both STC and RTC more efficiently decreased accumulation of reactive oxygen species (ROS) than carnosine and trolox. Both STC and RTC were resistant toward hydrolytic degradation by human serum carnosinase. STC and RTC were concluded to demonstrate higher antioxidant capacity and better ability to prevent cerebellar neurons from ROS accumulation than their precursors, carnosine and trolox.     

Synthesis and Antifungal Activity of Curcumol Derivatives

To discover novel and effective antifungal candidates, a series of new curcumol derivatives were designed, synthesized, and evaluated their antifungal activity against five phytopathogenic fungi by the mycelium growth rate method. Derivatives c4 , c22 and c23 exhibited excellent antifungal activity against Phomopsis sp. with EC₅₀ values of 3.06, 3.07, and 3.16 μM, respectively. Specifically, compound c4 exhibited the strongest antifungal activity against Phomopsis sp., which was 44 times that of pyrimethanil (EC₅₀=134.37 μM). The results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicated that compound c4 could cause cell senescence and death of Phomopsis sp. by changing the normal hyphal morphology and disrupting the normal metabolism of hyphal cells. Moreover, compound c4 showed excellent curative effect against Phomopsis sp. on kiwifruit. These findings confirmed that compound c4 has great potential as a potent antifungal agent.     

Synthesis and Cytotoxic Activity of Thiazolofluorenone Derivatives

The synthesis and biological evaluation of some novel thiazolofluorenones, thiazolofluorenes and thiazoloanthraquinones, substituted with amino side-chains are described. These polyheterocyclic compounds have been synthesized via the corresponding imino-1,2,3-dithiazoles. Their cytotoxic activity and their eventual selective effect on a phase of the cell cycle were evaluated in vitro, using the murine lymphocytic L1210 leukaemia cell line.     

Studies on the Phenylphenol Derivatives with Biological Activity

A number of compounds structurally related to phenylphenols were systematically synthesized as herbicides. Some of nitro-substituted derivatives show strong activity in pre-emergence test. The herbicidai activity of this series appears to relate with the pK-value of the compound.

Herbicidai activities of chloro-substituted phenylphenols were investigated. The derivatives of o-phenylpbenol and p-phenylphenol exhibited different selective toxicity between radish and rice, the latter appeared to have a specific inhibitory activity against the root growth of rice. As an attempt to analyze the correlation of herbicidai activity and chemical structure, the dissociation constant and the substituent constant π were applied in this investigation. The herbicidai activity correlated linearly with pK-value.     

Studies on the Phenylphenol Derivatives with Biological Activity

More than ninety phenylphenol derivatives were tested for fungistatic activity toward ten species of agriculturally important fungi. One of N-methylcarbamates and some nitro- or chloro-substituted derivatives were highly toxic against Piricularia oryzae. From the relationship between the chemical structure and the activity, it is supposed that the reactivity, the permeability, the steric effect and the metabolic activation of the compound are the responsible factors for the fungistatic activity.