Study on the quantitative structureactivity relation-ship of C-10 substituted artemisinin (QHS)’s derivatives using rough set theory

The structure-activity relationship study of C-10 substituted artemisinin (QHS) derivatives that are used as antimalarial was performed with the RS (rough sets) method. An RS process is a concise nonlinear process, and it has broad application foreground in the data mining of nonlinear life courses. In this work, initially the parameters of C-10 substituted QHS’s derivatives were computed with the quantum chemistry method, and the information table was constructed from the parameters (condition attributes) and biological activity (decision attributes). Based on the analysis of rough set theory, the core and reduction of attributes sets were obtained. Then the decision rules were extracted and the struc-ture-activity relationship was analyzed. As a nonlinear system, RS theory can extract the special rela-tion in the database. It has the advantage of being nonlinear over multiple linear regression (MLR), principal component analysis (PCA), partial least square (PLS), etc., and the advantage of obtaining results with unambiguous physical meanings over artificial neuron networks (ANNs), etc. The result obtained in this study is instructive to the study of pharmacodynamics, resistance mechanism of QHS and development of QHS’s derivatives.     

Synthesis,biological evaluation and molecular docking study of pyrimidine based thiazolidinone derivatives as potential anti-urease and anti-cancer agents

Hybrid analogs containing molecules are always the choice of different synthetic researcher due to their diverse biological applications and significantly more efficient. Heterocyclic being a good inhibitors against varied disease are most commonly used in drug designing and development. The current study also addressed the synthesis of pyrimidine-based thiazolidinone derivatives (1–13) using stepwise processes and their structure was confirmed using various characterization techniques such as ¹HNMR, ¹³CNMR, and HREI-MS. Furthermore, the biological significances of the synthesized scaffolds were also explored and proved to be as anti-urease and anti-cancer moieties. Their inhibitory potentials were determined using the minimum inhibitory concentration (MIC) in the presence of their standard drugs, Thiourea (IC₅₀ = 8.20 ± 0.20 µM) and Tetrandrineb (IC₅₀ = 12.30 ± 0.10 µM) respectively. Structure activity relationship (SAR) was established for all the synthesized scaffolds and compared their inhibitory potentials in which scaffolds 3 (IC₅₀ = 2.30 ± 0.30 and 3.20 ± 0.50 µM), 6 (IC₅₀ = 3.10 ± 0.20 and 6.20 ± 0.10 µM), 7 (IC₅₀ = 3.20 ± 0.20 and 3.80 ± 0.30 µM) and 10 (IC₅₀ = 4.20 ± 0.20 and 5.10 ± 0.30 µM) exhibited the most influential activity. These compounds were subsequently examined using molecular docking experiments, which evaluate the binding interaction of ligands with enzyme active sites.     

Synthesis,Characterization and In Vitro Evaluation of Novel 5-Ene-thiazolo[3,2-b][1,2,4]triazole-6(5H)-ones as Possible Anticancer Agents

The present paper is devoted to the search for drug-like molecules with anticancer properties using the thiazolo[3,2-b][1,2,4]triazole-6-one scaffold. A series of 24 novel thiazolo-[3,2-b][1,2,4]triazole-6-ones with 5-aryl(heteryl)idene- and 5-aminomethylidene-moieties has been synthesized employing three-component and three-stage synthetic protocols. A mixture of Z/E-isomers was obtained in solution for the synthesized 5-aminomethylidene-thiazolo[3,2-b]-[1,2,4]triazole-6-ones. The compounds have been studied for their antitumor activity in the NCI 60 lines screen. Some compounds present excellent anticancer properties at 10 μM. Derivatives 2h and 2i were the most active against cancer cell lines without causing toxicity to normal somatic (HEK293) cells. A preliminary SAR study had been performed for the synthesized compounds.     

Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity

Harringtonolide (HO), a natural product isolated from Cephalotaxus harringtonia, exhibits potent antiproliferative activity. However, little information has been reported on the systematic structure−activity relationship (SAR) of HO derivatives. Modifications on tropone, lactone, and allyl positions of HO (1) were carried out to provide 17 derivatives (2–13, 11a–11f). The in vitro antiproliferative activity against four cancer cell lines (HCT-116, A375, A549, and Huh-7) and one normal cell line (L-02) was tested. Amongst these novel derivatives, compound 6 exhibited comparable cell growth inhibitory activity to HO and displayed better selectivity index (SI = 56.5) between Huh-7 and L-02 cells. The SAR results revealed that the tropone and lactone moieties are essential for the cytotoxic activities, which provided useful suggestions for further structural optimization of HO.     

Isolation,Structure Elucidation and In Silico Prediction of Potential Drug-Like Flavonoids from Onosma chitralicum Targeted towards Functionally Important Proteins of Drug-Resistant Bad Bugs

Admittedly, the disastrous emergence of drug resistance in prokaryotic and eukaryotic human pathogens has created an urgent need to develop novel chemotherapeutic agents. Onosma chitralicum is a source of traditional medicine with cooling, laxative, and anthelmintic effects. The objective of the current research was to analyze the biological potential of Onosma chitralicum, and to isolate and characterize the chemical constituents of the plant. The crude extracts of the plant prepared with different solvents, such as aqueous, hexane, chloroform_, ethyl acetate, and butanol, were subjected to antimicrobial activities. Results corroborate that crude (methanol), EtoAc, and n-C₆H₁₄ fractions were more active against bacterial strains. Among these fractions, the EtoAc fraction was found more potent. The EtoAc fraction was the most active against the selected microbes, which was subjected to successive column chromatography, and the resultant compounds 1 to 7 were isolated. Different techniques, such as UV, IR, and NMR, were used to characterize the structures of the isolated compounds 1–7. All the isolated pure compounds (1–7) were tested for their antimicrobial potential. Compounds 1 (4′,8-dimethoxy-7-hydroxyisoflavone), 6 (5,3′,3-trihydroxy-7,4′-dimethoxyflavanone), and 7 (5′,7,8-trihydroxy-6,3′,4′-trimethoxyflavanone) were found to be more active against Staphylococcus aureus and Salmonella Typhi. Compound 1 inhibited S. typhi and S. aureus to 10 ± 0.21 mm and 10 ± 0.45 mm, whereas compound 6 showed inhibition to 10 ± 0.77 mm and 9 ± 0.20 mm, respectively. Compound 7 inhibited S. aureus to 6 ± 0.36 mm. Compounds 6 and 7 showed significant antibacterial potential, and the structure–activity relationship also justifies their binding to the bacterial enzymes, i.e., beta-hydroxyacyl dehydratase (HadAB complex) and tyrosyl-tRNA synthetase. Both bacterial enzymes are potential drug targets. Further, the isolated compounds were found to be active against the tested fungal strains. Whereas docking identified compound 7, the best binder to the lanosterol 14α-demethylase (an essential fungal cell membrane synthesizing enzyme), reported as an antifungal fluconazole binding enzyme. Based on our isolation-linked preliminary structure-activity relationship (SAR) data, we conclude that O. chitralicum can be a good source of natural compounds for drug development against some potential enzyme targets.     

Anti-Melanogenic Properties of Velutin and Its Analogs

Velutin, one of the flavones contained in natural plants, has various beneficial activities, such as skin whitening, as well as anti-inflammatory, anti-allergic, antioxidant, and antimicrobial activities. However, the relationship between the structure of velutin and its anti-melanogenesis activity is not yet investigated. In this study, we obtained 12 velutin derivatives substituted at C5, C7, C3′, and C4′ of the flavone backbone with hydrogen, hydroxyl, and methoxy functionalities by chemical synthesis, to perform SAR analysis of velutin structural analogues. The SAR study revealed that the substitution of functional groups at C5, C7, C3′, and C4′ of the flavone backbone affects biological activities related to melanin synthesis. The coexistence of hydroxyl and methoxy at the C5 and C7 position is essential for inhibiting tyrosinase activity. However, 1,2-diol compounds substituted at C3′ and C4′ of flavone backbone induce apoptosis of melanoma cells. Further, substitution at C3′ and C4′ with methoxy or hydrogen is essential for inhibiting melanogenesis. Thus, this study would be helpful for the development of natural-derived functional materials to regulate melanin synthesis.     

新型含三唑的烯丙基苯甲酸酯类化合物的合成及杀菌活性研究

为了寻找高杀菌活性的农药先导化合物,设计合成了一系列未见文献报道的含三唑的烯丙基苯甲酸酯类化合物,其结构经1H NMR和HRMS进行了确证,用X射线单晶衍射测定了(R,S)-(Z)-1,3-二苯基-2-(1H-1,2,4-三唑-1-基)烯丙基2,3-二氯苯甲酸酯(5j)的晶体结构.生物活性测定结果表明,在50 mg/L的浓度下,(R,S)-(Z)-1,3-二苯基-2-(1H-1,2,4-三唑-1-基)烯丙基苯甲酸酯(5a),(R,S)-(Z)-1,3-二苯基-2-(1H-1,2,4-三唑-1-基)烯丙基2-氟苯甲酸酯(5g)和(R,S)-(Z)-1,3-二苯基-2-(1H-1,2,4-三唑-1-基)烯丙基3-甲基苯甲酸酯(5n)对油菜菌核的抑菌率均达到了70%以上,显示出了较高的杀菌活性.     

Design,synthesis and bioactivity of chalcones and its analogues

The Vernohia anthelmintica L.'s extract is one of the most popular Uygur medicines used for vitiligo. It is believed that the chalcone compounds of the plant play an important role in the treatment since they may activate tyrosinase and improve melanin production. In this study, twenty-one chalcones and nine analogues were synthesized in view of three different components of chalcone(A, B ring and a,b-unsaturated carbonyl). After biological evaluation of their activity on tyrosinase in cell-free systems,the result showed that most compounds(except polyhydroxy chalcones) possess activator effect on the tyrosinase, especially for 13a–15a, 20 a and 1b, which bearing a comparable activity to the positive control8-MOP. SAR of these tyrosinase activator was summed up for the first time as well. Finally, compound 13 a was found to increase melanin contents and tyrosinase activity 1.75 and 1.3 fold, respectively, compared with that of untreated murine B16 cells at the concentration of 40 mg/m L.