Synthesis,Biological Evaluation,Mechanism of Action and Quantitative Structure–Activity Relationship Studies of Chalcones as Antibacterial Agents

Forty‐eight chalcone analogs were synthesized and their in vitro antibacterial activity against Staphylococcus aureus NCIM 5021, Bacillus subtilis NCIM 2718, Phaseolus vulgaris NCIM 2813, Escherichia coli NCIM 2931, Salmonella typhi 2501 and Enterobacter aerogenes NCIM 5139 were evaluated by microdilution broth assay. Quantitative structure–activity relationships were developed for all the cases (r ² = 0.68–0.79; = 0.58–0.78; q ² = 0.51–0.68; F = 13.02–61.51). Size, polarizability, electron‐donating/withdrawing and hydrophilic nature of the molecule determine the activity against these Gram‐positive and Gram‐negative bacteria. Staphylococcus aureus was the most and S. typhi was the least hydrophobic of these organisms. These chalcones act better against more hydrophobic organisms. The more active chalcones have log P between 1.5 and 3. Compound 24 , one of the most active compounds, was found to act by damaging the cell wall of S. aureus. Slimicidal activity of five of the most active compounds ( 24 , 31 , 32 , 34 and 37 ) was found to be in the range of 48–60% against S. aureus and 40–54% against E. coli. A correlation was observed among the hydrophobicity of the compounds, hydrophobicity of the bacterial cell surface and the antibacterial activity of the compound.     

1,3,5-三取代吡唑类ALK5抑制剂的合成与生物评价研究

目的 设计合成1,3,5-三取代吡唑类化合物,并研究其对ALK5所介导的TGFβ信号通路的抑制活性,以期发现新型ALK5抑制剂。方法 先以取代的苯甲醛和4-乙酰苯甲腈为原料,合成取代的查儿酮,再与芳基肼或芳基肼盐酸盐反应生成1,3,5-三取代吡唑啉,然后氧化脱氢得到相应的1,3,5-三取代吡唑类化合物,最后对官能团做适当的变换,得到目标化合物。应用基于细胞的TGF-Smad2 检测评价了化合物的ALK5抑制活性。结果与结论 合成目标化合物29个,其结构均经过了核磁与质谱的确证,其中化合物6c显示有较好的ALK5抑制活性。     

Potential cytotoxic and apoptosis inducing agents: synthesis and evaluation of methoxy-substituted chalcones against human lung and cervical cancers

The role of methoxy group substitution in various positions in both the rings of chalcones on cytotoxicity profile was studied using various synthesized chalcones. The fluorine containing acetophenones when reacted with various methoxy-substituted benzaldehydes in the presence of 10 % sodium hydroxide solution gave the functionalized chalcones. All the synthesized chalcones were confirmed by spectral techniques like FTIR, ¹H NMR, ¹³C NMR, and HRMS studies. All the synthesized compounds were screened for their cytotoxicity against various cell lines. The promising compounds were analyzed for cell cycle analysis.     

Synthesis and in-vitro antimicrobial activity of secondary and tertiary amines containing 2-chloro-6-methylquinoline moiety

A number of secondary and tertiary amines bearing 2-chloro-6-methylquinoline were synthesized by nucleophilic substitution reaction of 3-(chloromethyl)-2-chloro-6-methylquinoline with substituted aromatic primary and secondary amines in presence of catalytic amount of triethylamine (TEA) and K(2)CO(3). All the compounds were characterized by combined use of IR, (1)H-NMR, (13)C-NMR, mass spectral data, and microanalyses. The newly synthesized quinolinyl amines were screened in vitro for their antifungal activity against Aspergillus niger MTCC 281, Aspergillus flavus MTCC 277, Monascus purpureus MTCC 369, Penicillium citrinum NCIM 768 and for antibacterial activity strains viz. Escherichia coli NCTC 10418, Staphylococcus aureus NCTC 65710, and Pseudomonas aeruginosa NCTC 10662 by agar diffusion technique. Results of the preliminary screening revealed that some of the compounds mainly those with electron withdrawing groups in the phenyl ring showed promising antifungal activity.     

Synthesis, docking studies and antioxidant activity of some chalcone and aurone derivatives

Chalcones and aurones are found to possess high antioxidant activity. They are known to inhibit tyrosinase enzyme involved in synthesis of melanin. A series of substituted chalcones and aurones have been synthesized and tested for their antioxidant activity. Postulated structures of the newly synthesized compounds are in agreement with their IR, ¹H NMR and MS. The docking study of this series of compounds was performed on crystal structure of tyrosinase from Bacillus megaterium using VlifeMDS 3.0 software. Antioxidant activity data obtained from four methods, i.e., DPPH free radical scavenging assay, iron chelating assay, reducing power assay and hydrogen peroxide scavenging assay, indicate that the activity increased with dimethylamino group on position 4/4′ of ring B as evident from the significant activities of SB7 and SB8 in case of chalcones and aurones, respectively. The poor activities of SB4 and SB5 in DPPH scavenging ability and reducing power assays could be because of presence of chloro group on B-ring. Furthermore, the activity is facilitated with the presence of hydroxyl group on A-ring (preferably on position 5/5′) in both chalcones and aurones.     

Synthesis and antimicrobial activity of novel tetrahydrobenzothienopyrimidines

Due to the rapidly growing number of resistant strains of bacteria, the search for antibacterial agents with new modes of action will always remain an important and challenging task. Thus, the reaction of 2-substituted or unsubstituted-4-(4-acetylanilino)-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidine derivatives 1-3 with the hydrazine derivatives, semi and/or thiosemicarbazides, provided the corresponding hydrazones 4-6 and semi and/or thiosemicarbazones 7-9. Claisen-Schmidt condensation of compounds 1 or 2 with the appropriate aldehyde yielded the chalcones 10, 11 which, when treated with hydroxylamine hydrochloride gave rise to the isoxazoline-containing compounds 12, 13. Furthermore, reacting the respective chalcones 10, 11 with different hydrazines, urea and/or thiourea, furnished compounds 14, 15, 16, and 17 respectively. Representative compounds were tested for their antimicrobial activity against Candida albicans and certain gram-positive and gram-negative bacteria. Their MICs were then determined. Compound 15e, showed a broad spectrum of activity while most of the other compounds showed varying antimicrobial activity.     

Pyrazole–coumarin and pyrazole–quinoline chalcones as potential antitubercular agents

Pyrazole, coumarin, and quinoline are medicinally important moieties. In this study, two series of novel pyrazole–coumarin chalcones and pyrazole–quinoline chalcones were synthesized using multiple-step reactions. All the synthesized compounds were well characterized using different spectroscopic techniques including ¹H and ¹³C nuclear magnetic resonance, high-resolution mass spectroscopy, and electrospray ionization–mass spectrometry. The compounds were evaluated for their antitubercular activity against the Mycobacterium tuberculosis H37Rv strain using the microplate Alamar Blue assay, and the minimal inhibitory concentrations (MIC) of the compounds were determined. Among the 32 tested compounds, compounds 3e , 3u , and 7h showed an MIC value of 3.125 µg/ml, and they were found to be nontoxic. Molecular docking studies of the compounds with the enzyme DprE1 revealed the probable mechanism of action. The chalcone derivatives exhibited binding affinity values between −7.047 and −9.353 kcal/mol. ADME parameters were predicted using the QikProp module of the Schrödinger software, and these compounds exhibited good pharmacological and oral absorption properties.     

磺胺的噻二嗪硫酮衍生物的合成及抑菌活性研究

利用药物化学骈合原理设计并合成了一系列新的3，5-二取代1，3，5-噻二嗪-2-硫酮类化合物，其结构被红外光谱与紫外光谱及元素分析所证实，抑菌活性试验显示了良好的抑菌活性．     

六环喜树碱衍生物的合成与抗肿瘤活性研究

目的研究在喜树碱类化合物A环9,10位上增加一个六元环后，所得衍生物的生物活性的变化情况。方法分别以10-羟基喜树碱和7-乙基-10-羟基喜树碱(SN-38)为原料,通过三或四步反应得到一系列相应的A环上修饰的喜树碱衍生物,用MTT法评价了它们的细胞毒活性，用小鼠肝癌H₂₂评价它们体内的肿瘤抑制率。结果5个六环喜树碱衍生物为目标化合物，10个衍生物为新化合物。结论喜树碱A环的9,10位增加一个“1,4-氧嗪-2-酮”六元环后，其抗肿瘤活性要比喜树碱或10-羟基喜树碱的活性降低。     

Synthesis and biological activity studies of furan derivatives

The organic compounds, 4-Ethyl-2,5,5-triphenyl-4,5-dihydrofuran-3-carbonitrile; 2,4,5-Triphenyl-5-propyl-4,5-dihydrofuran-3-carbonitrile; 4-Ethyl-5,5-diphenyl-2-thien-2-yl-4,5-dihydrofuran-3-carbonitrile; 2-(1-Benzofuran-2-yl-)-5-propyl-4,5-diphenyl-4,5-dihydrofuran-3-carbonitrile; 4-Ethyl-5,5-diphenyl-4,5-dihydro-2,2’-bifuran-3-carbonitrile, were synthesized and purified through column chromatography and preparative TLC. All compounds were characterized by IR, ¹H, ¹³C NMR, MS, and microanalysis. The in vitro antibacterial and antifungal activities of these compounds were investigated against some bacteria and fungi. The antibacterial and antifungal activities were measured by using the disc-diffusion method against gram-positive bacteria, i.e., Staphylococcus aureus ATCC 25923, Staphylococcus enteritidis ATCC1376, Psydomamonas aeruginosa ATCC 29212, Bacillus subtilis RSKK 244, Bacillus megaterium gram-negative bacteria Escherichia coli ATCC 27853, Listeria monocytogenes ATCC 7644, and as fungus Micrococcus Luteus NRRLB was used. All compounds in this study showed activity against test bacteria. Their antibiogram tests showed better results than some known antibiotics.     

环丙沙星衍生物的合成及抗菌活性研究

目的研究环丙沙星衍生物的合成及其抗菌活性。方法采用2-甲基-5-硝基咪唑、环丙沙星等为原料,通过亲核取代反应合成目的物；测定目的物的抗菌活性。结果设计、合成了9个新化合物,其结构经MS,¹H NMR和元素分析确证。化合物II, IV_C和 IV_D的体内抗菌活性较明显。结论化合物II, IV_C和 IV_D显示了一定的体内抗菌活性,值得进一步研究。     

Design, synthesis, antibacterial activity, and molecular docking studies of novel hybrid 1,3-thiazine-1,3,5-triazine derivatives as potential bacterial translation inhibitor

Some novel hybrid 1,3-thiazine-1,3,5-triazine derivatives were synthesized and tested for antibacterial activity. Compounds 8c and 8f were found active against Gram positive and Gram negative microorganisms. Molecular docking studies have been performed on eubacterial ribosomal decoding A site (Escherichia coli 16S rRNA A site) to rationalize the probable mode of action, binding affinity, and orientation of the molecules at the active site of receptor. The structures of all these newly synthesized compounds were confirmed by their elemental analyses and spectral data techniques viz. IR, (1) H NMR, (13) C NMR, and mass.     

Design, synthesis, and in vitro antibacterial screening of some novel 3-pentyloxy-1-hydroxyxanthone derivatives

A series of 3-pentyloxy-1-hydroxyxanthone derivatives were synthesized by four-step reactions: first cyclocondensation between salicylic acid and phloroglucinol in the presence of Eaton’s reagents, then alkylation with 1,5-dibromopentane, followed by nucleophilic substitution by different nucleophiles to obtain final compounds. Molecular structures of the synthesized compounds were elucidated by FT-IR, ¹H NMR, ¹³C NMR, mass spectral data, and elemental analysis. The in vitro antibacterial activity was evaluated by MIC determination using broth dilution method against representative three Gram-positive and three Gram-negative bacterial strains with reference to ofloxacin. All the synthesized compounds showed antibacterial activity; besides the compounds 7f and 7g showed better Gram-positive and Gram-negative antibacterial activities.     

(S)-5-乙酰胺甲基-3-［(4-取代胺甲基)苯基］-2-噁唑烷酮衍生物的合成及抗菌活性

目的研究噁唑烷酮类衍生物的合成及抗菌活性。方法以4-甲基-3-卤代苯胺为原料，经氯甲酸苄酯酰化、与(R)-丁酸缩水甘油酯环合、甲磺酰化、叠氮化、叠氮还原成胺、胺基乙酰化、苄位溴化得到中间体取代溴苄VIIIa和VIIIb。VIIIa和VIIIb与胺类化合物包括脂肪胺、芳香胺发生取代反应生成IXa和IXb；测定目标化合物的体外抗菌活性。结果设计、合成了51个新化合物，其结构经¹H NMR、元素分析或MS确证。并测定了它们的比旋光度等理化常数。化合物VIIb，IXa1，IXa2，IXa7，IXb1，IXb3，IXb10，IXb16和IXb23对G⁺菌有一定的活性，但不如对照品吗啉噁酮和诺氟沙星。结论在吗啉噁酮结构中苯环4位和吗啉基之间插入亚甲基，不能提高化合物的抗菌活性。     

磺胺噻二嗪硫酮衍生物的合成及其抑菌活性

利用药物化学骈合原理设计并合成了一系列新的３，５－二取代１，３，５－噻二嗪－２－硫酮类化合物，其结构经红外光谱，紫外光谱及元素分析证实，抑菌活性试验显示了良好的抑菌活性。     

Synthesis and Antibacterial and Antifungal Studies of Novel Nitrogen Containing Heterocycles from 5-Ethylpyridin-2-ethanol

A novel series of chalcones, pyrimidines and imidazolinone is described; chalcones (4a-o) were prepared from the lead molecule 4-[2-(5-ethylpyridin-2-yl)ethoxy]benzaldehyde. Pyrimidine (5a-o) derivatives were prepared from the reaction of chalcones and guanidine nitrate in alkali media. Imidazolinones (6a-o) were synthesized from reaction of pyrimidine and oxazolone derivatives (prepared by Erlenmeyer azlactone synthesis). The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, (1)H and (13)C NMR spectral data. All the products were screened against different strains of bacteria and fungi. Most of these compounds showed better inhibitory activity in comparison to the standard drugs.     

Synthesis and anti-HIV activity of N'-nicotinoyl--3-(4'-hydroxy-3'-methylphenyl)-5-[substituted phenyl]-2-pyrazolines

A series of N'-nicotinoyl-3-(4'-hydroxy-3'-methylphenyl)-5-(substituted phenyl)-2-pyrazolines were synthesized by the reaction between isoniazid (INH) and chalcones and were tested for their in vitro anti-HIV activity. Among them, compound (c) showed a promising anti-HIV activity in vitro against used strains (IIIB, ROD), with IC50 of both IIIB 5.7 microM and ROD 7.0 microM.