Synthesis and Anticancer Activity Evaluation of Some Thienopyrimidine Derivatives

Russian Journal of Bioorganic Chemistry - The current study focused on effective and straightforward routes for preparing a new series of thieno[2,3-d]pyrimidine derivatives in addition to their...     

Design,Synthesis and Anticancer Evaluation of New Substituted Thiophene-Quinoline Derivatives

A series of new isoxazolyl, triazolyl and phenyl based 3-thiophen-2-yl-quinoline derivatives were synthesized adopting click chemistry approach. In addition, the synthesis of new useful synthon, (2-chloroquinolin-3-yl) (thiophen-2-yl) methanol, is reported. The obtained compounds were characterized by spectral data analysis and evaluated for their anticancer activity. All the derivatives were subjected to in vitro MTT cytotoxicity screening assay against a panel of four different human cancer cell lines, liver (HepG-2), colon (HCT-116), human cervical cancer (HeLa) and breast (MCF-7). Out of a library of 17 compounds, two compounds have been identified as potent and selective cytotoxic agents against HeLa and MCF-7 cell lines. SAR studies for such hybridized analogues were investigated and phenyl derivatives were proved to be more potent than isoxazole and triazole derivatives. Furthermore, the promising compounds were selected for in vitro inhibition of EGFR-TK and Topo II enzymes. Also, they were subjected to cell cycle arrest analysis and apoptosis assay on MCF-7 cells. Our recent finding highlights these thiophene-quinoline analogues as a promising class of compounds for further studies concerning new anticancer therapies.     

Anticancer and Antimicrobial Activities of Some Antioxidant-Rich Cameroonian Medicinal Plants

Traditional remedies have a long-standing history in Cameroon and continue to provide useful and applicable tools for treating ailments. Here, the anticancer, antimicrobial and antioxidant activities of ten antioxidant-rich Cameroonian medicinal plants and of some of their isolated compounds are evaluated.The plant extracts were prepared by maceration in organic solvents. Fractionation of plant extract was performed by column chromatography and the structures of isolated compounds (emodin, 3-geranyloxyemodin, 2-geranylemodin) were confirmed spectroscopically. The antioxidant activity (AOA) was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) bleaching method, the trolox equivalent antioxidant capacity (TEAC), and the hemoglobin ascorbate peroxidase activity inhibition (HAPX) assays. The anticancer activity was evaluated against A431 squamous epidermal carcinoma, WM35 melanoma, A2780 ovary carcinoma and cisplatin-resistant A2780cis cells, using a direct colorimetric assay. The total phenolic content in the extracts was determined spectrophotometrically by the Folin–Ciocalteu method. Rumex abyssinicus showed the best AOA among the three assays employed. The AOA of emodin was significantly higher than that of 3-geranyloxyemodin and 2-geranylemodin for both TEAC and HAPX methods. The lowest IC₅₀ values (i.e., highest cytotoxicity) were found for the extracts of Vismia laurentii, Psorospermum febrifugum, Pentadesma butyracea and Ficus asperifolia. The Ficus asperifolia and Psorospermum febrifugum extracts are selective against A2780cis ovary cells, a cell line which is resistant to the standard anticancer drug cisplatin. Emodin is more toxic compared to the whole extract, 3-geranyloxyemodin and 2-geranylemodin. Its selectivity against the platinum-resistant A2780cis cell line is highest. All of the extracts display antimicrobial activity, in some cases comparable to that of gentamycin.     

Synthesis and Antimicrobial Activity of Some New Coumarin and Dicoumarol Derivatives

Russian Journal of Bioorganic Chemistry - Phase transfer catalysis reaction of 4-hydroxy-6-methyl-2H-chromen-2-one with alkyl halides afforded C4 oxygen alkylation products of 2H-chromen-2-one...     

Synthesis and Evaluation of Novel Metacetamol Derivatives with Hydrazone Moiety as Anticancer and Antimicrobial Agents

By exploiting the wide biological potential of the hydrazone scaffold, a series of hydrazone derivatives were synthesized, starting from N-(3-hydroxyphenyl)acetamide (metacetamol). The structures of the compounds were determined using IR, ¹H and ¹³C-NMR, and mass spectroscopic methods. The obtained molecules ( 3 a – j ) were evaluated for their anticancer potential against MDA-MB-231 and MCF-7 breast cancer cell lines. According to the CCK-8 assay, all tested compounds showed moderate to potent anticancer activity. Among them, N-(3-(2-(2-(4-nitrobenzylidene)hydrazinyl)-2-oxoethoxy)phenyl)acetamide ( 3 e ) was found to be the most effective derivative with an IC₅₀ value of 9.89 μM against MDA-MB-231 cell lines. This compound was further tested for its potential effects on the apoptotic pathway. Molecular docking studies was also carried out for 3 e in the colchicine binding pocket of tubulin. Additionally, compound 3 e also demonstrated effective antifungal activity, particularly against Candida krusei (MIC=8 μg/ml), indicating that nitro group at the 4^th position of the phenyl ring was the most preferable substituent for both cytotoxic and antimicrobial activity. Our preliminary findings suggest that compound 3 e could be exploited as a leading structure for further anticancer and antifungal drug development.     

Synthesis and Antimicrobial and Antifungal Activity of Resin Acid Acetylene Derivatives

Russian Journal of Bioorganic Chemistry - A series of diterpenes that contain the morpholine, pyrrolidine, benzyl, nitrophenyl, and 1,2,3-tetrazole heterocyclic fragments have been synthesized from...     

New Benzopyrrole Derivatives: Synthesis and Appraisal of Their Potential as Antimicrobial Agents

A series of twenty compounds ( 23 – 42 ) were synthesized and characterized by spectral studies in order to explore newer antimicrobial compounds. The majority of the synthesized compounds reported significant antimicrobial properties against various pathogenic bacterial and fungal strains with the help of tube dilution method. Significant activities (MIC ranging from 3.9 to 15.62 μg/ml) have been shown against Gram-negative and Gram-positive bacteria with. In contrast, moderate to outstanding antibacterial activity was reported versus Gram-negative bacteria such as E. coli and P. aeruginosa along with Gram-positive bacteria such as S. aureus and B. subtilis. While antifungal activity was moderate to excellent against two fungus strains (Candida tropicalis, Candida glabrata). Compounds 25 and 34 had the utmost activity versus Gram-positive and Gram-negative bacteria too. The antifungal activity of compound 35 was comparable to that of standard. In-silico Molecular docking evaluations were performed for antibacterial and antifungal activities against the target DNA gyrase A (PDB: 1AB4) and 14 alpha-sterol demethylase enzyme (PDB: 1EA1), respectively. The dock score for typicals compounds for antibacterial and antifungal activity were −4.733 and −9.4, respectively. The three-dimensional QSAR examination was carried out by multiple linear regression (SA-MLR) with good predictive power (r2=0.9105, q2=0.8011). Establishment of several interactions between the ligand 25 and 34 and the active site of residue of both receptors, enable the ligand 25 and 34 to be fit well in the pocket of the active site, as seen in Molecular dynamics simulations analysis. Thus, data suggest that these ligands could be further explored as potential precursors to develop antimicrobial drugs.     

Synthesis and Antifungal Activities of Trichodermin Derivatives as Fungicides on Rice

Twenty new trichodermin derivatives, 2a – 5 , containing alkoxy, acyloxy, and Br groups in 4‐, 8‐, 9‐, 10‐ and 16‐positions were synthesized and characterized. The antifungal activities of the new compounds against rice false smut (Ustilaginoidea virens), rice sheath blight (Rhizoctonia solani), and rice blast (Magnaporthe grisea) were evaluated. The results of bioassays indicated that the antifungal activities were particularly susceptible to changes at 4‐, 8‐, and 16‐positions, but low to changes at 9‐ and 10‐positions. Most of these target compounds exhibited good antifungal activities at the concentration of 50 mg l^?1. Compound 4 (9‐formyltrichodermin; EC₅₀ 0.80 mg l^?1) with an CHO group at 9‐position displayed nearly the same level of antifungal activity against Ustilaginoidea virens as the commercial fungicide prochloraz (EC₅₀ 0.82 mg l^?1), while compound 3f ((8R)‐8‐{[(E)‐3‐phenylprop‐2‐enoyl]oxy}trichodermin; EC₅₀ 3.58 and 0.74 mg l^?1) with a cinnamyloxy group at C(8) exhibited much higher antifungal activities against Rhizoctonia solani and Magnaporthe grisea than the commercial fungicides prochloraz (EC₅₀ 0.96 mg l^?1) and propiconazole (EC₅₀ 5.92 mg l^?1), respectively. These data reveal that compounds 3f and 4 possess high antifungal activities and may serve as lead compounds for the development of fungicides in the future.     

白皮锦鸡儿黄酮醇类化合物及其抗菌和抗氧化活性(英文)

从豆科植物白皮锦鸡儿(Caragana leucophloea Pojark.)地上部分分离到3个黄酮醇类化合物,经理化和波谱分析鉴定为3-O-甲基山奈酚(1)、3-O-甲基槲皮素(2)和槲皮素(3)。活性测定表明,1表现出较强的抗细菌活性,对大肠杆菌和番茄疮痂病菌的半抑制浓度分别为9.00μg/mL和7.42μg/mL,最低抑制浓度均为12.5μg/mL;而2和3则表现出较强的抗氧化活性,对DPPH还原的半抑制浓度分别为14.39μg/mL和13.64μg/mL;对β-胡萝卜素-亚油酸氧化的半抑制浓度分别为10.26μg/mL和9.87μg/mL。上述黄酮醇类化合物均为首次从白皮锦鸡儿中分离得到。     

Synthesis of New Lathyrane Diterpenoid Derivatives from Euphorbia lathyris and Evaluation of Their Anti‐Inflammatory Activities

Euphorbia factor L₃, a lathyrane diterpenoid extracted from Euphorbia lathyris, was found to display good anti‐inflammatory activity with very low cytotoxicity. To find more potent anti‐inflammatory drugs, two series of Euphorbia factor L₃ derivatives with fatty and aromatic acids were designed and synthesized. Among them, lathyrane derivative 5n exhibited most potent inhibition on LPS‐induced NO production in RAW264.7 cells with no obvious cytotoxicity. To determine the key characteristics of Euphorbia factor L₃ derivatives that contribute to anti‐inflammatory activity, we conducted a structure‐activity relationship study of these compounds.     

Synthesis of New Furanone Derivatives with Potent Anticancer Activity

Russian Journal of Bioorganic Chemistry - New compounds based on Furanone derivatives were synthesized by reaction of 3-(4-nitrobezylidine)-5-phenylfuran-2(3H)-one with various reagents as...     

Synthesis of Schiff Bases and Secondary Amines with Indane Skeleton; Evaluation of Their Antioxidant,Antibiotic, and Antifungal Activities

In this study, Schiff bases were synthesized by utilizing the reaction of 4- and 5-aminoindane with substituted benzaldehydes. After the reduction of isolated Schiff bases with NaBH₄, the corresponding secondary amine derivatives were obtained. The structures of all synthesized molecules were confirmed by ¹H-NMR, ¹³C-NMR, FT-IR, and ESI-MS. Antioxidant activities of all synthesized molecules were investigated by DPPH method, and IC₅₀ values were calculated. In addition, antibacterial activities of targets were investigated by the well diffusion method, and then MIC99 values were calculated. While only four of the sixteen synthesized molecules showed a high level of antioxidant activity, all of the molecules exhibited biological activity against Gram-positive and Gram-negative bacteria to varying degrees. In addition, all the synthesized molecules showed high antifungal activity. In antioxidant capacity studies, the IC₅₀ values of 2-(((2,3-dihydro-1H-inden-5-yl)amino)methyl)-6-methoxyphenol ( 4 d ) and 2-(((2,3-dihydro-1H-inden-4-yl)amino)methyl)-6-methoxyphenol ( 7 d ) were determined to be 18.1 μg and 35.1 μg, respectively, and these values are much stronger than BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole) used as positive controls. The fact that targets have the same core structure with different substituents has revealed a good structure-activity relationship.     

Synthesis of Some New N-Substituted Imidazole Derivatives and Their In Vitro Antibacterial Investigation

Russian Journal of Bioorganic Chemistry - Here we reported the synthesis of N-substituted imidazole derivatives (VIa–o) that involves Suzuki coupling reaction between...     

Synthesis,Biological Evaluation,and Molecular Modeling Studies of New 1,3,4-Thiadiazole Derivatives as Potent Antimicrobial Agents

In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using ¹H-NMR, ¹³C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 μg/mL of the compounds 3f and 3g , respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds’ theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f .     

Synthesis of Novel Aryloxyethylamine Derivatives and Evaluation of Their in Vitro and in Vivo Neuroprotective Activities

A series of aryloxyethylamine derivatives were designed, synthesized and evaluated for their biological activity. Their structures were confirmed by ¹H‐NMR, ¹³C‐NMR, FT‐IR and HR‐ESI‐MS. The preliminary screening of neuroprotection of compounds in vitro was detected by MTT, and the anti‐ischemic activity in vivo was tested using bilateral common carotid artery occlusion in mice. Most of these compounds showed potential neuroprotective effects against the glutamate‐induced cell death in differentiated rat pheochromocytoma cells (PC12 cells), especially for (4‐fluorophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone, {1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}(4‐methoxyphenyl)methanone, (4‐bromophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone, {1‐[2‐(4‐chlorophenoxy)ethyl]piperidin‐4‐yl}(4‐chlorophenyl)methanone, (4‐chlorophenyl)(1‐{2‐[(naphthalen‐2‐yl)oxy]ethyl}piperidin‐4‐yl)methanone, (4‐chlorophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone and {1‐[2‐(4‐bromophenoxy)ethyl]piperidin‐4‐yl}(4‐chlorophenyl)methanone, which exhibited potent protection of PC12 cells at three doses (0.1, 1.0, 10 μM). Compounds (4‐fluorophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone, (4‐fluorophenyl){1‐[2‐(naphthalen‐2‐yloxy)ethyl]piperidin‐4‐yl}methanone, {1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}(4‐methoxyphenyl)methanone and {1‐[2‐(4‐chlorophenoxy)ethyl]piperidin‐4‐yl}(4‐chlorophenyl)methanone possessed the significant prolongation of the survival time of mice subjected to acute cerebral ischemia and decreased the mortality rate at all five doses tested (200, 100, 50, 25, 12.5 mg/kg) and had significant neuroprotective activity. In addition, (4‐fluorophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone, {1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}(4‐methoxyphenyl)methanone and {1‐[2‐(4‐chlorophenoxy)ethyl]piperidin‐4‐yl}(4‐chlorophenyl)methanone possessed outstanding neuroprotection in vitro and in vivo. These compounds can be used as a promising neuroprotective agents for future development of new anti‐ischemic stroke agents. Basic structure–activity relationships are also presented.     

Design,Synthesis, and Antifungal Activities of Novel 1,2,4‐Triazole Schiff Base Derivatives

With the aim to find new compounds with high antifungal activity, 21 4‐amino‐5‐substituted‐1,2,4‐triazole Schiff bases ( 2a  –  2g , 3a  –  3g , and 4a  –  4g ) were designed and synthesized. Their antifungal activities against Pythium solani, Gibberlla nicotiancola, Fusarium oxysporium f. sp. niveum, Gibberlla saubinetii, Alternaria iycopersici, Phytophthora capsici, Physalospora piricola, Cercospora arachidicola hori, and Fusarium oxysporium f. sp. cucumber were tested, parts of the compounds exhibited excellent antifungal activity. This research provides useful information for further study of antifungal agents.     

The Synthesis and Antiviral Activity of Some New S-Adenosyl-L-homocysteine Derivatives and Their Nucleoside Precursors

Abstract

S-Adenosyl-L-homocysteine (SAH) and some of its analogues are potent inhibitors of transmethylation reactions catalysed by S-adenosyl methionine dependent methyltransferases.¹     

Synthesis,Antimicrobial Activities,and Molecular Docking Studies of Dihydrotriazine Derivatives Bearing a Quinoline Moiety

In this article, three series of dihydrotriazine derivatives bearing a quinoline moiety ( 5a , 5b , 8a – 8c , and 9a – 9m ) have been designed, synthesized, and evaluated as antibacterial agents. Compounds 8a – 8c were found to be the most potent of all of the compounds tested with an MIC value of 1 μg/mL against several Gram‐positive (S. aureus 4220 and MRSA CCARM 3506) and Gram‐negative (E. coli 1924) strains of bacteria. In addition, 3‐[4‐amino‐6‐(phenethylamino)‐2,5‐dihydro‐1,3,5‐triazin‐2‐yl)‐6‐[(3‐chlorobenzyl)oxy]quinolin‐2‐ol ( 8a ) showed potent inhibitory activity (MIC=2 μg/mL) against Pseudomonas aeruginosa 2742, indicating that its antibacterial spectrum is similar to those of the positive controls gatifloxacin and moxifloxacin. Structure‐activity relationships (SAR) analyses and docking studies implicated the dihydrotriazine group in increasing the antimicrobial potency of the quinoline compounds. In vitro enzyme study implied that compound 8a also displayed DHFR inhibition.     

异黄酮衍生物的设计、合成与抗肿瘤活性

为了提高大豆苷元的生物利用度以改善其抗肿瘤活性,利用前药原理对大豆苷元进行修饰。本文根据前药原理成功设计合成了5个新型大豆苷元磺酸酯衍生物（3～7）,所有化合物的结构均经IR、MS、元素分析和。HNMR确证。体外细胞初步活性筛选试验结果表明,部分标题化合物也具有一定的抗肿瘤活性。     

姜黄素衍生物的合成及抑菌活性研究

以含有杂原子的生物素、硫辛酸、异烟酸和姜黄素为原料,以二步酰氯法合成了姜黄素生物素酯、姜黄素硫辛酸酯、姜黄素异烟酸酯.经红外,核磁共振氢谱和质谱确证了化合物的结构.在相同条件下,以姜黄素为对照测定了产物对金色葡萄球菌的抑菌性能.结果显示,姜黄素硫辛酸酯、姜黄素生物素酯、姜黄素异烟酸酯三种姜黄索衍生物在抑菌活性上均有不同程度的增强,最小抑菌浓度(MIC)分别为2.5、5.0、5.0 mg/mL,在最小抑菌浓度下抑菌圈分别为10、10、8 mm.