Synthesis of new water soluble diorganotin(IV) complexes with hydrazones derived from Girard-T reagent as antibacterial and anticancer agents

Three new water-soluble organotin complexes R₂Sn(5-BrSalGT)Cl [R = Ph, Me] and Ph₂Sn(2-OHNaphGT)Cl have been synthesized by the reaction of R₂SnCl₂ (R = Ph or Me) with Schiff bases derived from condensation of Girard-T reagent with 5-bromosalicylaldehyde and 2-naphthaldehyde, (5-BrH₂SalGT)Cl (1) and (2-OHH₂NaphGT)Cl (2). The synthesized compounds have been investigated by elemental analysis, conductometric measurements, IR, ¹H NMR, and ¹¹⁹Sn NMR spectroscopy. These data show that the deporotonated ligand is coordinated to Sn(IV) via ONO atoms and six-coordinate zwitterionic complexes are formed. The ligands and their complexes were investigated for their in vitro toxicity against Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. The results show remarkable antibacterial activity against the studied bacteria. All complexes exhibit more inhibitory effects than the parent ligand. The anticancer activity of all compounds were also performed on HN5 cell line and (2-OHH₂NaphGT)Cl with concentration of 1 mg mL^?1 was found to show higher anticancer activity than other compounds.     

Synthesis and biological activity evaluation of new thiazolidinone-diclofenac hybrid molecules

Abstract

A novel series of [2-(2,6-dichlorophenylamino)-phenyl]-acetic acid N`-3-(substituted)-4-thiazolidin-5-ylidenemethyl-hydrazide derivatives has been designed and synthesized. The structures of synthesized compounds were confirmed by their <sup>1</sup>H NMR, <sup>13</sup>C NMR and LCMS spectroscopic data. Target compounds were screened for their in vitro anticancer activity according to US NCI protocols, in vitro trypanocidal activity toward Trypanosoma brucei brucei (Tbb) and evaluated for anti-inflammatory activity on the carrageenan edema model in rats. Biological screening data led to identification of compounds 3.3 ([2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid N`-(4-oxo-2-thioxo-thiazolidin-5-ylidenemethyl)-hydrazide) and 3.7 ([2-(2,6-dichloro-phenylamino)-phenyl]-acetic acid N`-(4-oxo-2-thioxo-3-(3-trifluoromethylphenyl)thiazolidin-5-ylidenemethyl)-hydrazide) which demonstrated moderate antitumor activity on the non-small-cell lung cancer NCI-H522 and colon cancer HCT-116 cell lines. Several hit compounds (3.2, 3.4) exhibited the promising and significant inhibition growth of the parasites at micromolar concentrations (IC₅₀ values of 4.8 and 7.06?μM, respectively). The synthesized compounds also demonstrated considerable anti-inflammatory effect comparable to the reference non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac sodium or ketorolac tromethamine.     

Synthesis,biological evaluation and molecular docking studies of novel 2-(2-cyanophenyl)-N-phenylacetamide derivatives

A series of novel 2-(2-cyanophenyl)-N-phenylacetamide derivatives 3(a-u) were designed and synthesized via selective amidation of methyl-2-(2-cyanophenyl)acetates over amidine formation by using AlMe₃ as catalyst in good yields. All the newly synthesized derivatives were well characterized by ¹H NMR, ¹³C NMR, FTIR and HRMS spectral techniques. All the synthesized title compounds were evaluated for their in vitro anticancer activity against three cancer cell lines. Among all compounds, 3i (IC₅₀?=?1.20 μM, IC₅₀?=?1.10 μM), 3j (IC₅₀?=?0.11 μM, IC₅₀?=?0.18 μM), 3o (IC₅₀?=?0.98 μM, IC₅₀?=?2.76 μM) showed excellent inhibitory activity than the standard Etoposide (IC₅₀?=?2.11 μM, IC₅₀?=?3.08 μM) against MCF-7 and A-549 cell lines, respectively. Docking analysis of all the compounds with the human topoisomerase II revealed that the compound 3j fitted well in the active site pocket, showing the best docking score of 158.072 kcal/mol.

     

Design,Synthesis, and Evaluation of the Anticancer Properties of a Novel Series of α‐(Benzoylamino)‐β‐substituted Acrylic Amide Derivatives of Pyrazolo[1,5‐a]pyrimidine

A novel series of α‐(benzoylamino)‐β‐substituted acrylic amide derivatives of pyrazolo[1,5‐a]pyrimidine has been synthesized using a convergent multistep synthesis. The synthesized compounds were characterized by ¹H NMR, ¹³C NMR, ESI‐MS, and IR analyses. Those new compounds were screened for their in vitro antiproliferative activity using an MTT assay analysis. Out of nine derivatives synthesized in the current study, compounds 13g , 13d , 13h , and 13i exhibited the greatest anticancer activities in HeLa and HepG₂ cell lines. The in vitro anticancer activity of compound 13g against HeLa, HepG₂, and MCF‐7 cell lines is superior to the marketed drugs paclitaxel and SAHA.     

Synthesis of novel 1,3-thiazin-4-ones by acetylene diester cyclization and their anticancer activities

A novel series of 1,3-thiazin-4-one derivatives containing a piperidyl ring (7–16) were designed and synthesized efficiently by thioamide and acetylene diester cyclization reaction via aminolysis of the ester group and the elimination of an alcohol molecule. The structures of all the novel compounds were established by their FTIR, Mass, ¹H NMR, and ¹³C NMR spectral techniques. The newly synthesized compounds (7–16) were studied for their in vitro anticancer activity against human liver cancer cell lines Hep G2 using MTT assay. The IC₅₀ values of the tested compounds were ranging in between 7.48 ± 0.71 and 56.57 ± 1.37 µM. Further, the apoptosis evaluation by the mitochondrial membrane potential using JC-1 dye was carried out and the results are in good agreement with the cytotoxicity studies.     

Design,Synthesis, and Evaluation of the Anticancer Properties of a Novel Series of Imidazolone Fused Pyrazolo[1,5‐a]pyrimidine Derivatives

A novel series of imidazolone fused pyrazolo[1,5‐a]pyrimidine derivatives has been designed and synthesized using a convergent approach, and the structures of these compounds were confirmed by ¹H NMR, ¹³C NMR, ESI‐MS, and IR analyses. These new compounds were tested for their in vitro antiproliferative activity using an 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. Out of the 20 derivatives prepared in the current study, compounds 8h , 8n , and 8r exhibited good anticancer activities tested against HeLa cells and HepG₂ cells. However, the in vitro anticancer activity of compound 8r against HeLa, HepG₂, and MCF‐7 cell lines is superior to the marketed drugs Paclitaxel and SAHA.     

Heteroleptic Pd(II) dithiocarbamates: synthesis,characterization, packing and in vitro anticancer activity against HeLa cell line

Two new heteroleptic Pd(II) dithiocarbamates (1 and 2) have been synthesized by reaction of equimolar quantities of palladium(II) chloride, sodium 4-(3-methoxyphenyl)piperazine-1-carbodithioate, and appropriate substituted triphenylphosphines. The synthesized complexes have been characterized by their physical, spectral (IR, ¹H, ¹³C, and ³¹P NMR), and X-ray crystallographic data. Complexes 1 and 2 showed square-planar geometry both in solution and solid states. The crystal packing of both complexes revealed similar 3-D-supramolecular networks comprised of 1-D chains. However, the nature and strength of various non-covalent interactions of these networks were slightly different. The DNA interaction studies of the complexes have been carried out by UV–visible spectroscopy to evaluate their anticancer potential. The study suggested intercalative interaction with 2.402 × 10⁴ and 2.713 × 10³ M^?1 binding constants, respectively. The complexes have also been evaluated for their anticancer activity against HeLa cell line. Both complexes showed higher activity with IC₅₀ values much lower (22.176 and 26.166 μM for 1 and 2, respectively) than the standard cisplatin (78.075 μM). Furthermore, the complexes induced stronger DNA fragmentation as investigated by DNA ladder assay for apoptosis. Our findings suggested that the anticancer action of these compounds stems from their interaction with DNA leading to DNA damage and apoptosis. The excellent activity of 1 and 2 deserves to be a focus for further research and in vivo studies.     

合成硅氧醚的新方法：Silyltriflimides与醇或与醚反应

首次利用silyltriflimides［双－（三氟甲磺酰）－亚胺基硅烷］与醇或醚反应合成了一系列非环链状或环状的硅氧醚,反应产率较好。其中反应物silyl triflimides很容易由相应的苯基硅烷或丙烯基硅烷与HNTf2通过质子脱硅化反应得到。合成的新化合物的结构用1H NMR, 13C NMR, MS, IR 和HRMS等进行了表征.     

1-烃基-2-(4-β-D-吡喃阿洛糖苷-苯基)-苯并咪唑类化合物的合成及其镇静活性的研究

以豆腐果苷为原料, 在冰醋酸催化下和邻苯二胺缩合生成中间体2-(4-β-D-吡喃阿洛糖苷-苯基)-苯并咪唑(2), 2与卤代烃在K₂CO₃作用下以乙醇为溶剂合成了一系列1-烃基-2-(4-β-D-吡喃阿洛糖苷-苯基)-苯并咪唑类化合物3a～3h. 新化合物2和3a～3h的结构经¹H NMR, IR和MS (HRMS)确认, 并对2和3a～3h进行了药理活性筛选. 结果表明, 部分化合物具有良好的镇静活性; 其中化合物2 (100 mg•kg^－1), 3f (100 mg•kg^－1)与豆腐果苷相比较具有更强的药理活性.     

Synthesis,ABTS-Radical Scavenging Activity,and Antiproliferative and Molecular Docking Studies of Novel Pyrrolo[1,2-a]quinoline Derivatives

A new 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)-radical scavenging and antiproliferative agents of pyrrolo[1,2-a]quinoline derivatives have been synthesized. An efficient method for the synthesis of 14 novel diversified pyrrolo[1,2-a]quinoline derivatives has been described using 4-(1,3-dioxolan-2-yl)quinoline and different phenacyl bromides in acetone and followed by reacting with different acetylenes in dimethylformamide/K₂CO₃. The structure of the newly synthesized compounds was determined by infrared, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. The in vitro antioxidant activity revealed that among all the tested compounds 5n exhibited maximum scavenging activity with ABTS. Compound 5b has showed good antiproliferative activity as an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase.     

A convenient synthesis and crystal structure of disubstituted 1,2,3-triazoles having ether functionality

Abstract

A series of 27 ether-linked 1,4-disubstituted 1,2,3-triazoles (8a–8z₁) has been synthesized by 1,3 dipolar cycloaddition of 1-substituted-4-(prop-2-yn-1-yloxy)benzene (3a–3c) and aromatic azides (5a–5c, 7a–7f). The synthesized compounds were explicated by FTIR, ¹H NMR, ¹³C NMR and HRMS techniques. The structures of synthesized triazoles 8c (CCDC 1840219) and 8f (CCDC 1840220) were also confirmed by X-ray crystallography.     

Synthesis of novel substituted pyridines from 1-(3-aminophenyl)-3-(1<Emphasis Type="Italic">H</Emphasis>-indol-3-yl)prop-2-en-1-one and their anticancer activity

A series of novel substituted pyridine derivatives have been synthesized via the reaction of 3-indole carboxaldehyde with 3-aminoacetophenone. The products structures have been elucidated from elemental analysis as well as IR, ¹H NMR, ¹³C NMR, and MS spectroscopy data. All the synthesized compounds have shown anticancer activity against HEPG2 and MCF-7 in vitro; some of them have exhibited the in vivo activity.     

CeCl3·7H2O Catalyzed,Microwave-Assisted High-Yield Synthesis of α-Aminophosphonates and their Biological Studies

Abstract

A new class of diethyl(3,5-dibromo-4-hydroxyphenylamino) (substituted phenyl/heterocyclic) methylphosphonates 4(a–j) has been synthesized by one-pot three component simultaneous reaction (Kabachnik–Fields) of 4-amino-2,6-dibromophenol 1, substituted heterocyclic/phenyl aldehydes 2(a–j), and diethylphosphite 3 using a Lewis acid catalyst, CeCl₃·7H₂O (5 mol%) under microwave irradiation as well as conventional conditions. It was observed that microwave irradiation method is more facile, efficient, and advantageous with respect to reaction time and yields. The structures of all the synthesized compounds were supported by analyzing IR, ¹H/¹³C/³¹P NMR, and mass spectral data. The synthesized compounds were screened for their in vitro antimicrobial and antioxidant activities.     

Synthesis and biological evaluation of 1,2,4-oxadiazole linked 1,3,4-oxadiazole derivatives as tubulin binding agents

As an aspect of our ongoing research in search of new anticancer agents, a series of novel analogs of 1,3,4-oxadiazole embedded with 1,2,4-oxadiazole moieties (11a–j) were synthesized. The structure of the final compounds was confirmed by ¹H NMR, ¹³CNMR and mass spectroscopic techniques and evaluated for their in vitro anticancer activity against three human cancer cell lines (lung, breast). Among the synthesized compounds, 11?b, 11?g, 11?h, and 11i showed potent anticancer activity with IC₅₀ values within the range of 0.34?±?0.025 to 2.45?±?0.23?μM against three human cancer cell lines. Further, these compounds (11a–j) were investigated for molecular docking studies. Among them, compound 11?h showed strong binding affinity on binding sites of target protein EGFR (PDB ID: 4hjo) with highest docking score (-7.028). It revealed that 11?h was a strong tubulin binding agent.     

Time-dependent AI-Modeling of the anticancer efficacy of synthesized gallic acid analogues

Background/AimMain objective of this study is mapping of the anticancer efficacy of synthesized gallic acid analogues using modeling and artificial intelligence (AI) over a large range of concentrations and exposure times to explore the underline mechanisms of drug action and draw careful inferences regarding drug response heterogeneity.MethodsTwo series of gallic acid derivatives i.e. esters and amides have been synthesized and characterized by FTIR, NMR and mass spectrometry. The compounds have been tested in vitro for their anticancer activity against wild type human ovarian cancer cell line A2780, prostate cancer cell line PC3 and normal human fibroblast cells 3T3. To completely characterize optimal anticancer activity, a comprehensive model using piecewise recursive Hill model is used to quantitatively assess the in vitro anticancer effect of the tested compounds as a function of concentration and exposure time for periods ranging from 24 to 72 h. A robust artificial intelligence approach i.e. the “Support Vector Machine (SVM) Learning Algorithm” is adopted to utilize the data obtained at different temporal values, to identify compounds that trail forecasting algorithm.ResultsAll the synthesized analogues were found biocompatible. Significantly low EC₅₀ values indicated that tested compounds have potent anticancer activity against A2780 cell line in comparison to PC3 cells where only few compounds generated same impact at almost 200 times high dose. On the basis of EC₅₀ values, compounds 7 h, 7 m, 9c, 9b, 7c, 7b and 7 g were identified as the most active anticancer agent against A2780. Three major patterns of drug response heterogeneity were observed for different compounds in the form of multiple Hill graphs and shallow slopes. The anticancer efficiency of the compounds was verified using Machine learning SVM regression learner algorithm. For compounds 7a, 7b, 7e, 7 g, 7o, 7 r, 9b, 9e-9 g higher accuracy was found in predicted and experimentally obtained end point potency in terms of % viability.ConclusionsPharmacodynamics modeling of anticancer potential of the synthesized compounds revealed that drug efficacy and response heterogeneity could be modulated by changing the exposure time to optimize therapeutic impact. Combining experimental results with AI based drug action forecasting, compounds 7b, 7 g, and 9b may be tested further as potent anticancer agent for in vivo studies. This approach may serve a useful tool for extrapolation of in vitro results for generating lead compounds in in vivo and preclinical studies.     

Design and synthesis of fluorescent symmetric bis-triazolylated-1,4-dihydropyridines as potent antibreast cancer agents

Herein, we report the synthesis of fluorescent 1,4-dihydropyridine-linked bis-triazoles (2a–2n) through Hantzsch synthesis by the condensation of o/m-chloro-substituted benzaldehyde, ethyl 3-oxo-4(prop-2-yn-1-yloxy)butanoate, and ammonium acetate in the presence of Ba(NO₃)₂ as a catalyst followed by the click reaction of resultant Hantzsch product (1) with various aromatic as well as aliphatic azides. All the synthesized compounds were well characterized by ¹H-NMR, ¹³C-NMR, FTIR, and HRMS spectral techniques. Antibreast cancer evaluation of all the synthesized derivatives revealed that the compounds 2f (IC₅₀?=?7?±?0.02?µM) and 2g (IC₅₀?=?5?±?0.03?µM) showed better anticancer activity (lower IC₅₀) than the standard drug tamoxifen (IC₅₀?=?11.2?±?0.01?µM) against breast carcinoma (MDA-MB-231) cell line. The synthesized compounds were also screened against normal human embryonic kidney (HEK-293) cell line and found to be nontoxic. The fluorescent nature and cytotoxicity assay of these newly synthesized hybrids recommend their utility in tumor cell imaging.     

The Utility of Isothiocyanato Thiophenes in the Synthesis of Thieno[2,3-d]pyrimidine Derivatives as Possible Radioprotective and Anticancer Agents

The synthesis of novel thioureido derivatives 3, 8, and 10; biscompounds 7, 9, and 11; and tetracyclic compounds 5, 6, and 16 utilizing 5-isothiocyanato-3-methyl-thiophene-2,4-dicarboxylic acid diethyl ester 2 are reported. The structures of these compounds were confirmed by microanalyses and IR, ¹H NMR, and mass spectroscopy. Preliminary biological studies of some of the synthesized compounds showed promising radioprotective and anticancer activities.     

有机锡9-芴酮-4-甲酸酯的合成、结构及抗癌活性

合成了 3 个有机锡 9-芴酮-4-甲酸酯:三苯基锡 9-芴酮-4-甲酸酯[(C₆H₅)₃Sn(C₁₄H₇O₃)] (1)、三环己基锡 9-芴酮-4-甲酸酯[(C₆H₁₁)₃Sn(C₁₄H₇O₃)] (2)和三(2-甲基-2-苯基丙基)锡 9-芴酮-4-甲酸酯[(C₆H₅C(CH₃)₂CH₂)₃Sn(C₁₄H₇O₃)] (3)。通过元素分析、红外光谱、核磁共振谱(¹H、¹³C和 ¹¹⁹Sn)、热重分析进行了表征;用单晶X射线衍射方法测定了化合物的晶体结构,并对其进行了量子化学计算和体外抗癌活性研究。结果显示:化合物1为一维链状结构,中心锡原子为五配位的畸变三角双锥构型;化合物2和3均为单核分子,锡原子均为四配位的畸变四面体构型。化合物对人宫颈癌细(HeLa)、人肝癌细胞(HUH-7)、人非小细胞肺癌细胞(A549)、人肺腺癌细胞(H1975)和人乳腺癌细胞(MCF-7)都有较好的抑制活性。     

Novel Bis(1,2,4-oxadiazolyl) Fused Thiazole Derivatives: Synthesis and Anticancer Activity

A novel series of bis-1,2,4-oxadiazole fused benzothiazole derivatives 9a–9j are synthesized, and their structures are confirmed by ¹H and ¹³C NMR, and mass spectral data. All products are evaluated in vitro for their anticancer potential against a panel of four human cancer cell lines such as lung cancer (A549), breast carcinoma (MCF-7), melanoma (A375), and colon cancer (HT-29). The combretastatin-A4 is used as standard drug. All compounds 9a–9j exhibit significant anticancer activity with IC₅₀ values ranging from 0.11±0.01 to 14.6±3.89 μM. Among these, compounds 9a–9d, 9h, 9i demonstrate more potent activity than the control.

     

Click synthesis of new 7-chloroquinoline derivatives by using ultrasound irradiation and evaluation of their biological activity

This study describes the click synthesis of new 7-chloroquinoline derivatives by using ultrasound irradiation and evaluation of their activity as antimicrobial, antimalarial and the anticancer. All the compounds show moderate antimalarial activity with IC₅₀?<?100?μM, six of them showed high antimalarial activity (2, 3, 4, 6, 8 and 9) with IC₅₀?<?50?μM. The most active 7-chloroquinoline derivative is a compound (9). Also, the newly synthesized compounds were screened for their antitumor activity towards three lines of cancer cells, MCF-7 (human breast cancer), HCT-116 (colon carcinoma) and Hela (Cervical carcinoma) cell lines. Compounds (3) and (9) exerted the highest activity on all cell lines and showed special selectivity toward MCF-7 cells and the antibacterial screening data showed moderate to good inhibition zone (12.5?±?0.63–23.8?±?1.5) towards all the tested compounds. Elucidation of the structures of these new pure compounds was based on, IR, ¹H NMR, ¹³C NMR, MS and their elemental analysis.