Antimycobacterial and antioxidant activities of reserpine and its derivatives

In view of the attributed medicinal properties of reserpine, a number of acyl reserpine derivatives were prepared and tested for antimycobacterial activity against Mycobacterium tuberculosis, strain H(37)Rv and antioxidant activities. The results indicated that in the case of antimycobacterial activity, 10 out of 18 derivatives caused more inhibition than that caused by reserpine itself. The results of antioxidant activity revealed that acylation in benzene ring of reserpine decreases the percentage inhibition of DPPH in all the derivatives compared to the parent compound (1).     

The relationship between the antimicrobial activity of eugenol and the LPETG peptide structure and associated analysis for docking purposes

Sortase A is responsible for the virulence of Gram-positive pathogens, including staphylococci and streptococci. The LPETG is the peptide surface anchor signal for Sortase A. The inhibitors of this enzyme shared similar binding pattern with substrate LPETG. Eugenol and its derivatives may act as sortase A inhibitor. The antimicrobial activity of eugenol and its derivatives was tested in vitro against bacterial strains: Staphylococcus aureus, Streptococcus mutans and Escherichia coli. All the tested derivatives demonstrated antimicrobial activity. Differences between derivatives in terms of in vitro activity and interactions between the amino acid residues were correlated in the docking analysis for the same derivatives. According to the relationship observed in this study between the antimicrobial activity of eugenol and the LPETG peptide structure, some of the eugenol derivatives proved to be more active inhibiting sortase A than eugenol against microorganisms when tested at the same concentrations.     

Synthesis and anti-HIV-1 activity of the conjugates of gossypol with oligopeptides and D-glucosamine

A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV- 1I activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosamine not only reduced the cytotoxicity of gossypol derivatives but also enhanced their antiviral activity against HIV-1. Interestingly, D-glucosamine derivative of gossypol that lacked the COONa group also exhibited the same potent anti-HIV-1 activity as oligopeptide derivatives with the COONa group. These compounds blocked the entry of HIV-1ⅢB into target cell. which was similar to T20. Furthermore, the molecular docking analysis rationalized their anti-HIV-1 activity. The results also implied that certain oligopeptides and D-glucosamine were important moities to prepare gossypol derivatives as HIV- 1 entry inhibitors besides certain amino acids.     

Synthesis and antimicrobial evaluation of new 2-pyridinone and 2-iminochromene derivatives containing morpholine moiety

As trail to overcome on the antimicrobial drug-resistance problems, new functionalized 2-pyridinone and 2-iminochromene derivatives bearing morpholine moiety were designed and synthesized. The 2-pyridinone derivatives were obtained through the cyclization of cyanoacetohydrazone of 4-morpholinylacetophenone with 1,3-dicarbonyl compounds, α,β-unsaturated nitriles or 2-(arylidene)malononitriles. The 2-iminochromene derivatives were synthesized through the ring closure of cyanoacetohydrazonewith salicylaldehyde derivatives. The antibacterial and antifungal activities for the synthesized 2-pyridinone and 2-iminochromene derivatives were investigated. Most of the tested compounds showed moderate activity against P. vulgaris. Compounds 4a,b and 5a,b showed moderate activity against G −ve bacteria. All iminochromene derivatives showed moderate activity against C. albicans. Compound 8c was the most active compound.     

Synthesis and Antitubercular,Antimicrobial, and Hemolytic Activity of Methyl D-Glucopyranuronate and Its Simplest Derivatives

Methyl glucuronate and some of its simplest derivatives have been synthesized, and their antitubercular, antimicrobial, and hemolytic activities have been studied. The simplest derivatives of glucuronic acid have been shown for the first time to exhibit a high antitubercular activity which is comparable with the activity of isoniazid.     

Synthesis of some new pyrimidine derivatives and evaluation of their anticancer and antibacterial activities

Starting from the reaction of ethyl cyanoacetate with thiourea and the appropriate aldehydes, a series of new pyrimidine derivatives were prepared. Ten selected pyrimidine derivatives were subjected to a screening system for the investigation of their antitumor potency against liver (HEPG2) cell line. The antitumor activity results indicated that most of the selected pyrimidine derivatives showed moderate growth inhibition activity against the tested cell line, but with varying intensities in comparison to the known anticancer drugs: 5-fluorouracil and doxorubicin. Some of the synthesized compounds were also tested for their antimicrobial activity against bacteria as well as fungal isolates.     

Synthesis and platelet aggregation inhibitory activity of diphenylazole derivatives. I. Thiazole and imidazole derivatives

Diphenylimidazole and diphenylthiazole derivatives were synthesized and tested as inhibitors of platelet aggregation in in vitro experiments with the rabbit. Diphenylthiazole derivatives (10) were more potent than diphenylimidazole derivatives (4) in inhibiting arachidonic acid-induced platelet aggregation of rabbit platelet-rich plasma. Two diphenylimidazole and eight diphenylthiazole derivatives were evaluated for ex vivo arachidonic acid and collagen-induced platelet aggregation inhibitory activity using guinea pigs. In these compounds, 4,5-bis(4-methoxyphenyl)-2-(1,5-dimethyl-2-pyrrolyl)thiazole (10n) showed strong activity in vitro and ex vivo. The ex vivo activity of 10n was 200 times stronger than that of aspirin. The mechanism of the activity of 10n was the inhibition of cyclo-oxygenase.     

Design,synthesis and antibacterial activity of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain

A series of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain have been designed and synthesized. In vitro antibacterial activity evaluation showed that most of the derivatives exhibited potent antibacterial activity against drug resistant Gram-positive strains. Compounds 12a, 12d, and 28 are the most active derivatives in this series, displaying activity comparable to that of retapamulin and BC-3781. As the metabolic stability of this series is not satisfactory, further modifications are going on to improve their pharmacokinetic profile.     

6-取代喹唑啉衍生物的合成及抗肿瘤活性研究进展

喹唑啉及其衍生物作为重要的药效团,具有广谱的抗肿瘤生物活性,一直是药物化学研究的热点。本文围绕近年来6-酰胺类、卤代类、醚类、与7-位成环类、杂环类等喹唑啉衍生物的合成及其抗肿瘤活性作用机制研究进行概述,以期为活性更高、毒性更小的新型抗肿瘤化合物的设计合成提供参考。     

Light-energy conversion systems for hydrogen production and photocurrent generation using zinc chlorin derivatives

To develop efficient systems for light-energy conversion, monomeric and dimeric zinc chlorin derivatives were synthesized. These derivatives act as photosensitizers for light-induced hydrogen production with methylviologen as the electron mediator and Pt nanoparticles as the hydrogen-evolution catalyst. The monomeric derivative exhibited ~1.5-times higher activity than the dimeric derivative. The photocurrent-generating activity of the Zn chlorin derivatives assembled on a chemically modified indium tin oxide electrode was investigated; the dimeric derivative exhibited significant activity compared to the monomeric derivative. The photosensitizing activity of the derivatives in dye-sensitized solar cells was also investigated. The dimeric derivative exhibited two-fold higher performance than the monomeric derivative. The dimerization effect on the photosensitizing activities is briefly discussed in terms of stacking conformations based on the results of absorption and fluorescence spectroscopies.     

Triaryl-1,3,5-triazinane-2,4,6-triones (Isocyanurates) Peripherally Functionalized by Donor Groups: Synthesis and Study of Their Linear and Nonlinear Optical Properties

The linear optical (LO) and nonlinear optical (NLO) properties of a series of isocyanurates functionalized by donor arms at the periphery are reported herein. These octupolar derivatives were obtained in a straightforward way from commercial isocyanate derivatives and were fully characterized. Although several of these compounds are known, those that exhibited the largest NLO activities are all new compounds. In terms of second-order activity, several of these derivatives exhibit remarkable activity/transparency tradeoffs. In terms of third-order activity, the longer derivatives with the stronger donor groups (X=NH(2) , NMe(2) , or NPh(2) ) were shown to possess significant two-photon absorption cross sections. These strongly luminescent derivatives exhibit two-photon absorption cross sections up to 410?GM. DFT computations were also conducted to unravel their electronic structures and to rationalize their NLO properties. To our knowledge, the present study is the first concerned with the nonlinear optical properties of these original cyclotrimers.     

Antioxidant Activity of Sesamol Derivatives and Their Drug Delivery via C60 Nanocage: a Theoretical Study

The antioxidant activity of sesamol derivatives and their drug delivery via fullerene were investigated. Fullerene can interact with sesamol derivatives, and their adsorptions were possible from the energetic viewpoint. Adding the NH_2 group to sesamol can improve the sensitivity of sesamol toward fullerene surface. The NH_2 and OMe substitutions increase the antioxidant activity of sesamol. The results can also be used to select novel sesamol derivatives with higher antioxidant activity and higher drug delivery ability.     

Studies on cardiotonic agents. II. Synthesis of novel phthalazine and 1,2,3-benzotriazine derivatives

A series of phthalazine and 1,2,3-benzotriazine derivatives which have heterocyclylpiperidino groups was synthesized and tested for cardiotonic activity in anesthetized dogs. Several 6,7-dimethoxyphthalazine derivatives showed relatively potent cardiotonic activity comparable to that of amrinone.     

Polymeric Derivatives of Chloramphenicol and Their Antibacterial Properties

The polymerizable derivatives of chloramphenicol were prepared and free-radical copolymerized with acrylamide, methacrylic acid, and 2-(dimethylamino)ethyl methacrylate in order to obtain polymers with pharmacological activity. The monomeric and polymeric derivatives were subjected to antibacterial activity tests against Bacillus polymyxa.     

L-苯丙氨酸衍生物的一锅法合成及其抗/促凝活性

氨基酸及其衍生物在止血/抗凝活性方面有一定的应用。以L-苯丙氨酸为起始原料,经磺化引入磺酸基,再与甲醇、乙醇、丙醇、异丙醇和正丁醇脱水酯化,一锅法合成了6种未见报道的L-苯丙氨酸的磺酸酯类衍生物(L1~L6),以期获得具有的较强血液生理活性的潜在药物。实验中采用了质谱、核磁共振进行结构表征。该合成方法产率高(78%~95%),后处理简单,不失为合成该类衍生物的好方法。衍生物的凝血四项实验表明:抗促凝效果是内源性和外源性凝血途径共同作用的结果。血浆复钙实验表明:衍生物均具有一定的抗凝活性,其抗凝效果随浓度变化而变化,但是随R链的长度增加,抗凝效果并未见规律性。衍生物的抗凝活性主要受磺酸基及酯基的影响,因此在设计合成抗血栓化合物时可以考虑引入磺酸基及酯类基团。     

Synthesis and antibacterial activity of Schiff bases of 5-substituted isatins

Based on the existing reports on the bioactive isatin derivatives, a number of Schiff bases were synthesized by reacting 5-substituted isatins with bioactive amines/hydrazides and their structures were confirmed using spectroscopic methods such as NMR, IR and mass spectrometry. Furthermore, Nbenzylation of isatin followed by the Schiff base formation furnished a new series of compounds(11a–13c) which allowed the analysis of the effect of isatin N-substitution on the bioactivity of the resulting compounds. The antibacterial activity of the synthesized derivatives was evaluated using a microtiter plate method on a series of gram positive and gram negative bacterial strains. Compounds 2d, 3b, 5c and 6a were among the most potent derivatives against Pseudomonas aeruginosa(MIC = 6.25 μg/m L).Analysis of the structure–activity relationship showed that the incorporation of(thio)urea-based Schiff bases lead to more potent derivatives with a broader spectrum of antibacterial activity. In addition,highly lipophilic compounds such as 11a–12c did not show any measurable antibacterial activity, which implies that an optimal lipophilicity might be an important requirement for the antibacterial activity of the studied isatins. Finally, the finding that hydantoin derivatives of N-benzylisatins(13a–13c) still exhibit some antibacterial activity prompted us to consider exploring the bioactivity of more diverse derivatives of isatin-aminohydantoin Schiff bases(compounds 1a–1d) in our future studies.     

Exploring the potential of xanthene derivatives as trypanothione reductase inhibitors and chloroquine potentiating agents

Xanthene derivatives were synthesized and evaluated for their potential as trypanothione reductase (TryR) inhibitors and chloroquine (CQ) potentiating agents. Some derivatives displayed inhibitory activity against TryR comparable to known tricyclic anti-depressants. On the other hand a number of derivatives increased CQ accumulation and potentiating effects in a resistant strain of Plasmodium falciparum with one compound also displaying strong intrinsic antimalarial activity.     

取代噻吩双酰胺类化合物的设计、 合成及生物活性

利用中间体衍生化方法, 将噻吩环引入到双酰胺类化合物中, 合成了一系列取代噻吩双酰胺类化合物1~3; 目标化合物的结构经核磁共振波谱、 红外光谱及元素分析确认. 生物活性测试结果表明, 化合物1在600 mg/L剂量下对小菜蛾具有良好的杀虫效果, 致死率均为100%, 其中化合物1a和1e在20 mg/L剂量下对小菜蛾的致死率仍达到60%以上; 改变双酰胺结构中的吡唑环得到化合物2和3, 其杀虫活性消失, 说明该类化合物中吡唑环结构对杀虫活性具有关键作用.     

哥纳三醇类似物抗A2780肿瘤细胞活性及三维定量构效关系研究

以合成的54个哥纳三醇类似物为研究对象, 测试了其体外抑制肿瘤A2780细胞株的活性, 对其中的37个化合物用比较分子力场(CoMFA)研究了哥纳三醇类似物结构与抑制A2780肿瘤细胞活性的三维定量构效关系, 提出了对哥纳香醇甲结构改造的方法, 对寻找更好活性的化合物有重要的指导意义     

Microwave-Assisted Synthesis,Biological Activity Evaluation,Molecular Docking,and ADMET Studies of Some Novel Pyrrolo [2,3-b] Pyrrole Derivatives

Novel pyrrolo [2,3-b] pyrrole derivatives were synthesized and their hypolipidemic activity was assessed in hyperlipidemic rats. The chemical structures of the new derivatives were confirmed through spectral analysis. Compounds 5 and 6 were revealed to be the most effective hypolipidemic agents, with considerable hypocholesterolemic and hypotriglyceridemic effects. They appear to be promising candidates for creating new powerful derivatives with anti-atherosclerotic and hypolipidemic properties. As for antimicrobial activity, some of the tested compounds showed moderate activity against Pseudomonas aeruginosa: compound 2 revealed an MIC value of 50 μg/mL, compared to 25 μg/mL for ciprofloxacin. Compound 3 showed good antimicrobial activity against Staphylococcus aureus, comparable to ciprofloxacin, and roughly half the activity of ampicillin, according to MIC values. Compound 2 has an MIC approximately 25% of that of clotrimazole against Candida albicans. Compound 2 also showed the highest antioxidant activity with 59% inhibition of radical scavenging activity. Additionally, the cytotoxic activity of these new derivatives 1–7 was investigated and most of them showed good anticancer activity against the three tested cell lines.