Utility of 6‐Amino‐2‐thiouracils as a Core of Biologically Potent Polynitrogen–Sulfur Fused Heterocycles

One pot three‐component reaction was assisted to form some new pyridopyrimidine derivatives to be investigated as antimicrobial and antitumor agents. The newly synthesized compounds showed high significant antimicrobial activity against the applied strains of both Gram‐positive and Gram‐negative bacteria and fungi. The cytotoxic activity of some compounds was evaluated as inhibitor of growth in both human liver carcinoma and breast cell lines. The results showed that some compounds exhibited very high cytotoxicity against human liver cell line and breast cancer cells.     

Synthesis,characterization and catalytic,cytotoxic and antimicrobial activities of two novel cyclotriphosphazene‐based multisite ligands and their Ru(II) complexes

Two novel cyclotriphosphazene ligands ( 2 and 3 ) bearing 3‐oxypyridine groups and their corresponding Ru(II) complexes ( 4 and 5 ) were synthesized and their structures were characterized using Fourier transform infrared, ¹H NMR and ³¹P NMR spectroscopic data and elemental analysis. The Ru(II) complexes were used as catalysts for catalytic transfer hydrogenation of p‐substituted acetophenone derivatives in the presence of KOH. Additionally, the cytotoxic activities of compounds 2 , 3 , 4 , 5 were evaluated against PC3 (human prostate cancer), DLD‐1 (human colorectal cancer), HeLa (human cervical cancer) and PNT1A (normal human prostate) cell lines. Finally the antimicrobial activities of compounds 2 , 3 , 4 , 5 were evaluated against a panel of Gram‐positive and Gram‐negative bacteria and yeast cultures. The complexes showed efficient catalytic activity towards transfer hydrogenation of acetophenone derivatives, especially those bearing electron‐withdrawing substituents on the para‐position of the aryl ring. The compounds were found to have moderate to high cytotoxic and antimicrobial activities, and Ru(II) complexation enhanced both cytotoxic and antimicrobial activities in comparison with the parent compounds. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthetic Approach to Some New Annulated 1,2,4‐Triazine Skeletons with Antimicrobial and Cytotoxic Activities

The synthesis of some triazolotriazine, tetrazolotriazine, triazinotetrazine, and triazinotetrazepino‐indole by the reaction of 4‐amino‐6‐benzyl‐3‐hydrazinyl‐1,2,4‐triazin‐5(4H)‐one ( 2 ) with different reagents is described. The synthesized compounds were screened for their antimicrobial activity using the minimum inhibition concentration method by serial dilution technique. Two of these compounds showed higher activity than that of standard drug, and they were further evaluated for their cytotoxic activities against human cancer cells (MCF‐7, HCT116, and HepG2), which indicate strong effect on these cancer cell lines.     

5-氟尿嘧啶-1-烷氧苯基三间氯苯基卟啉的合成及其体外抗癌活性

为提高5-氟尿嘧啶抗癌的靶向性,降低其不良反应,合成了5种新型卟啉-5-氟尿嘧啶衍生物及其Mn3+配合物,优化了合成反应条件,探索了目标化合物的分离方法。 通过IR、UV-Vis、1H NMR和ESI-MS对化合物结构和组成进行了确认。 采用四甲基偶氮唑蓝(MTT)比色法,以5-氟尿嘧啶为阳性对照药,测试了卟啉化合物对5种肿瘤细胞的体外抑制活性。 初筛结果显示,化合物D3对人卵巢癌细胞Sk-ov-3有较强的抑制作用。     

Synthesis of chalcones with anticancer activities

Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC?? values were chosen and studied in detail with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities (p < 0.05). The ROS level showed 1.3-fold increase (p < 0.05) at the low concentrations used and thus it was concluded that the compounds increased the ROS level eventually leading to apoptosis in MCF-7 cells through intrinsic as well as extrinsic pathways.     

Exploration of quinoxaline derivatives as antimicrobial and anticancer agents

Novel 2 and 3‐substituted quinoxaline derivatives were synthesized through various synthetic pathways, among which cyanoacetamide and cyanoacetohydrazide quinoxaline derivatives 4a‐c and 11a‐c , respectively, were synthesized. Furthermore, methoxy quinoxaline derivatives 3c and quinoxaline derivatives bearing substituted pyridines 6a,b , 12a,b , and 13a,b were designed to be synthesized. However, we have synthesized acrylohydrazide 5a,b and 7 /acrylamide derivatives, Schiff base analogues 14a‐f , pyrazole derivatives 15a‐e, amide derivatives 16a‐f , guanidine derivatives 16 g,h as well as, quinoxalin‐2‐methylallyl propionate derivative 14g . All the synthesized compounds were confirmed via spectral data and elemental analyses. Moreover, the newly synthesized compounds were evaluated for their antimicrobial activity (Gm +ve, Gm ?ve in comparison to Gentamycin a standard) and fungi (in comparison to Ketoconazole as a standard). Thus, compound 16b showed promising antimicrobial activity against B. subtilis, P. vulgaris, and S. mutants with values ranging from 20 to 27‐mm zone of inhibition. While compounds 5a , 14e,f, and 16a,c,d,g,h showed potent antimicrobial activity. Moreover, the National Cancer Institute (NCI) selected 20 compounds that were submitted for anticancer screening against 60 types of cancer cell lines. The most active compounds are 5b and 12a where compound 5b containing 2,4‐dichlorophenyl moiety at cyanoacetamide linkage of hydrazine quinoxaline backbone exerted significant growth inhibition activity against Leukemia MOLT‐4, Renal cancer UO‐31, and Breast cancer MCF‐7. In addition, compound 12a having 4,6‐diaminopyridinone side chain at position‐3 of quinoxaline nucleus exhibited remarkable anticancer activity against renal cancer UO‐31.     

Investigation and comparison of biological effects of regioselectively synthesized thiazole derivatives

In this study, anticancer, antibacterial (against hospital-isolated antibiotic-resistant Escherichia coli strains), antifungal, and antioxidant effects of synthesized heterocyclic compounds 5 and 7 containing thiazole core were examined. Cytotoxicity testing was utilized against MCF-7 breast cancer cells via MTT cell viability assay. Antibacterial and antifungal activities were checked out according to Clinical and Laboratory Standards Institute (CLSI) guidelines, and antioxidant properties were evaluated through scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals. Results showed the viability of breast cancer cell lines was reliant on concentration of heterocycles and time of incubation. Synthetic compounds exhibited excellent antibacterial and antifungal properties base on their minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) values as well as high antioxidant activities according to their IC₅₀ values. Higher anticancer and antibacterial properties were observed with compound 7; on the contrary, thiazole 5 had better antioxidant effects. They can be introduced as potent antimicrobial, antioxidant, and anticancer agents.     

Synthesis and in vitro antitumor activity of 1,3,4-thiadiazole derivatives based on benzisoselenazolone

A series of novel 1,3,4-thiadiazole derivatives based on benzisoselenazolone were synthesized and evaluated for their cytotoxicity in vitro against human liver cancer cell SSMC-7721,human breast cancer cell MCF-7 and human lung cancer cell A549 by CCK-8 assay.The results showed mat compounds 7e,7f,7h,7k,71 and 7m displayed good cytotoxicity against MCF-7 cell lines.Compound 71 exhibited the most potent antitumor activities among the tested compounds.     

Synthesis and cytotoxicity of indolopyrrolemaleimides

A series of indolopyrrolemaleimides have been synthesized and evaluated for their cytotoxicity in vitro against human leukemia cell line and four human solid cancer cell lines. Some of the compounds showed high or mediate activity against the lines. 6dc is the most promising compound among them. The inhibition toward topoisomerase I was also studied.     

Synthesis and Bioactivity Evaluation of New 6-Aryl-5-cyano Thiouracils as Potential Antimicrobial and Anticancer Agents

Several novel 6-aryl-5-cyano thiouracil derivatives were synthesized and explored for their activities as antibacterial, antifungal and anticancer agents. The antimicrobial evaluation revealed that compounds 7b and 7c possessed superior antibacterial activity against the Gram positive bacteria S. aureus and B. subtilis compared to the reference drug amoxicillin. Moreover, compound 4i was found to be a broad spectrum antimicrobial agent and it also exhibited the highest antifungal activity against C. albicans, even higher than the reference drug amphotericin B (MIC = 2.34, 3.00 μg/mL respectively). Selected compounds were tested for in vitro cytotoxicity at a single 10^-5 M concentration in accordance to the NCI (USA) protocol. The preliminary screening results showed that most of the compounds had limited cytotoxic activity against renal cancer UO-31 and/or A498 cell lines. Nevertheless, compounds 6d and 6i displayed potent growth inhibitory effect toward non-small cell lung cancer HOP-92 and leukemia MOLT-4 cell lines, respectively.     

Synthesis,Cytotoxic Activity Evaluation of Novel 1,2,3‐Triazole Linked Quinazoline Derivatives

A series of novel 1,2,3‐triazole‐quinazoline derivatives were synthesized in five steps starting from anthranilamide by conventional methods. All the title compounds 10a — 10r were evaluated for cytotoxic activity against four human cancer cell lines (MGC ‐803, EC ‐109, MCF ‐7 and HGC ‐27) using MTT assay in vitro . Some of the synthesized compounds exhibited moderate to potent activity against tested cancer cell lines. Among them, compounds 10 h and 10q exhibited excellent growth inhibition against HGC ‐27 and compound 10 m also possessed excellent activity against MCF ‐7, with IC₅₀ values less than 1 µmol/L. Especially, compound 10 h was more cytotoxic than 5‐fluorouracil against all tested four human cancer cell lines.     

Biological Activity of Newly Synthesized Benzimidazole and Benzothizole 2,5-Disubstituted Furane Derivatives

Newly designed and synthesized cyano, amidino and acrylonitrile 2,5-disubstituted furane derivatives with either benzimidazole/benzothiazole nuclei have been evaluated for antitumor and antimicrobial activity. For potential antitumor activity, the compounds were tested in 2D and 3D cell culture methods on three human lung cancer cell lines, A549, HCC827 and NCI-H358, with MTS cytotoxicity and BrdU proliferation assays in vitro. Compounds 5, 6, 8, 9 and 15 have been proven to be compounds with potential antitumor activity with high potential to stop the proliferation of cells. In general, benzothiazole derivatives were more active in comparison to benzimidazole derivatives. Antimicrobial activity was evaluated with Broth microdilution testing (according to CLSI (Clinical Laboratory Standards Institute) guidelines) on Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Additionally, Saccharomyces cerevisiae was included in testing as a eukaryotic model organism. Compounds 5, 6, 8, 9 and 15 showed the most promising antibacterial activity. In general, the compounds showed antitumor activity, higher in 2D assays in comparison with 3D assays, on all three cell lines in both assays. In natural conditions, compounds with such an activity profile (less toxic but still effective against tumor growth) could be promising new antitumor drugs. Some of the tested compounds showed antimicrobial activity. In contrast to ctDNA, the presence of nitro group or chlorine in selected furane-benzothiazole structures did not influence the binding mode with AT-DNA. All compounds dominantly bound inside the minor groove of AT-DNA either in form of monomers or dimer and higher-order aggregates.     

Antimicrobial and cytotoxic effects of Mexican medicinal plants

The antimicrobial effects of the Mexican medicinal plants Guazuma ulmifolia, Justicia spicigera, Opuntia joconostle, O. leucotricha, Parkinsonia aculeata, Phoradendron longifolium, P. serotinum, Psittacanthus calyculatus, Tecoma stans and Teucrium cubense were tested against several human multi-drug resistant pathogens, including three Gram (+) and five Gram (-) bacterial species and three fungal species using the disk-diffusion assay. The cytotoxicity of plant extracts on human cancer cell lines and human normal non-cancerous cells was also evaluated using the MTT assay. Phoradendron longifolium, Teucrium cubense, Opuntia joconostle, Tecoma stans and Guazuma ulmifolia showed potent antimicrobial effects against at least one multidrug-resistant microorganism (inhibition zone > 15 mm). Only Justicia spicigera and Phoradendron serotinum extracts exerted active cytotoxic effects on human breast cancer cells (IC50 < or = 30 microg/mL). The results showed that Guazuma ulmifolia produced potent antimicrobial effects against Candida albicans and Acinetobacter lwoffii, whereas Justicia spicigera and Phoradendron serotinum exerted the highest toxic effects on MCF-7 and HeLa, respectively, which are human cancer cell lines. These three plant species may be important sources of antimicrobial and cytotoxic agents.     

Synthesis of novel heptaplatin derivatives and evaluation of their ability to inhibit proliferation of cancer cell lines

A series of novel heptaplatin derivatives were synthesized and evaluated for their ability to inhibit growth of two cancer cell lines: human colon carcinoma cell line HCT-8 and human hepatocarcinoma cell line Bel-7402. Majority of the synthesized compounds demonstrated superior activity against cancer cell lines compared to heptaplatin. Specifically, compounds 5a and 5b (5 µg/mL) had more pronounced efficacy against the HCT-8 cell line while 6b and 6c (0.5 µg/mL) had higher efficacy against Bel-7402 cell line.     

Synthesis and Biological Evaluation of Novel 5,7-Diphenylimidazo[1,2-a]pyridine Derivatives

A series of novel 5,7-diphenylimidazo[1,2-a]pyridine derivatives was designed and synthesized. The in vitro cytotoxic activities of all the target compounds against human colorectal cancer（HT-29）, human lung can- cer（H460）, human gastric cancer（MKN45） and human breast cancer（MDA-MB-231） cell lines were evaluated. The pharmacological results indicated that most of the target compounds showed moderate to excellent activities against the tested cell lines. The most promising compound 4h（0.20, 0.006, 0.08, 0.021 μmol/L） was 2.6, 5.1, 3.6 and 21.9 times more active than EPC2407（0.52, 0.031, 0.29, 0.46 μmol/L） against HT-29, H460, MKN45 and MDA-MB-231 cell lines, respectively.     

Design,synthesis and docking studies of new hydrazinyl-thiazole derivatives as anticancer and antimicrobial agents

Increase in the number of infections caused by pathogenic microbes in cancer patients has prompted the searcher to invest in the development of agents having dual anticancer and antimicrobial properties. The present study is concerned with synthesis and screening for anticancer and antimicrobial activity of a series of 5-hydrazinyl-2-(2-(1-(thien-2-yl)ethylidene)hydrazinyl)thiazole derivatives. The structure elucidation of the synthesized hydrazinyl thiazole derivatives was illustrated by spectroscopic and elemental analysis. All the newly synthesized compounds 5a-p were evaluated for in-vitro cytotoxic activity against breast carcinoma (MCF-7 cell line), hepatocellular carcinoma (HePG-2) and colorectal cancer (HCT-116) cell lines using MTT assay method. Compounds 5 g, 5h showed broad spectrum activity against three cancer cell lines with IC₅₀ ranged from 3.81 to 11.34 µM in compared to the reference drug Roscovitine (IC₅₀ = 9.32 to 13.82 µM), while compounds 5 l and 5 m were found to be more selective against HePG-2 and HCT-116 cell line (IC₅₀ = 9.29 and 8.93 µM respectively) and compound 5j was more selective against HePG-2 and MCF-7 cell lines (IC₅₀ = 6.73 and 10.87 µM respectively). The inhibitory activity of the most promising compounds was tested against the EGFR and ARO enzymes and were further tested for apoptosis and Annexin V/PI staining. The results of enzyme-based tests revealed that the tested compound 5j has a dual inhibitory effect on the EGFR and ARO enzymes with IC₅₀ = 82.8 and 98.6 nM respectively in compared to the reference drugs Erlotinib and Letrozole (IC₅₀ = 62.4 and 79 nM respectively). Furthermore, the majority of the tested hydrazinyl thiazole derivatives exhibited significant antimicrobial activity against the used pathogenic microbes species. Compounds 4b, 5h, 5j and 5 m exerted a good antibacterial and antifungal activity against all tested pathogenic microbes. Therefore, it was concluded that compounds 5 h, 5j and 5 m proved to possess dual anticancer and antimicrobial agent and may serves as a useful lead compounds in search for further modification or derivatization to give more potent and selective agents.     

Facile synthesis and cytotoxicity of 5-C-alkylates of 20（S）- camptothecins

A series of 5-C-alkylating camptothecins have been synthesized by one-step method, and their in vitro antitumor activity was evaluated against six human cancer cell lines. The results showed that all 5-C-alkylates of camptothecins possessed poor cytotoxicity on six human cancer cell lines.     

Bioactive Fluorenes. Part II. Unprecedented biologically active thiazole derivatives based-2,7-dichlorofluorene as competent DHFR inhibitors: Design,synthesis, and molecular docking approaches

In this study, a new series of (4-(2,7-dichloro-9H-fluoren-4-yl)thiazol-yl)acetamide derivatives was synthesized, and the new heterocycles were completely characterized, evaluated for their antimicrobial activity, and screened for cytotoxic activity against human lung carcinoma (A-549) and human breast carcinoma (MCF-7) cell lines. A molecular docking study was undertaken to identify the possible mode of action of the synthesized compounds, which suggested binding interactions with the dihydrofolate reductase (DHFR) active sites.Most of the synthesized compounds displayed meaningful activity against A-549 and MCF-7 cell lines when compared to 5-fluorouracil (5-FU), which was used as a reference drug. Furthermore, some of the prepared compounds exhibited potent antibacterial and antifungal activities. The highly pronounced biological activities of the compounds under investigation offer such species as promising future drug prospects which may find applications in the fields of biological and medicinal sciences.     

Multistep synthesis and screening of heterocyclic tetrads containing furan,pyrazoline, thiazole and triazole (or oxadiazole) as antimicrobial and anticancer agents

In the present study novel heterocyclic tetrads containing furan, pyrazoline, thiazole and triazole (or oxadiazole) (1, 2, 3, 4a-e and 5a-e) were designed and synthesized and investigated for their antimicrobial (against selected bacteria and fungi) and anticancer potential. The molecules 4e and 5e containing 4-fluoro phenyl and 4-fluoro benzyl substituents showed promising antimicrobial (antibacterial and antifungal activities with MICs ranging between 0.5 and 8 µg/mL. Compounds 3 exhibited potent anticancer activity with an IC₅₀ value of 0.49 ± 1.45 µM against the human gastric cancer cell line (BGC-823) whereas compound 4e displayed an IC₅₀ value of 0.65 ± 0.53 µM against breast cancer (MCF-7) cell line respectively. All compounds showed selective toxicity against the cancer cell lines compared to human normal liver cell lines. Molecular docking studies of the most potent compounds (3 and 4e) against selected microbial and cancer proteins revealed the crucial binding interactions of the potent compounds with the target enzymes. Compounds 3 and 4e are promising lead molecules to be developed as potential drug candidates.     

1,3,4-噁二唑和1,3,4-噻二唑衍生物的设计、合成和生物活性研究

为了寻求新型抗肿瘤药物,设计并合成了一系列新型1,3,4-噁二唑和1,3,4-噻二唑衍生物,对这些化合物在人类四种癌细胞:B-16(皮肤黑色素瘤细胞)、PC-3(人前列腺癌细胞)、U87(人原发性胶质母细胞瘤细胞)和A549(人非小细胞肺癌细胞)进行抗肿瘤活性评价.结果显示部分化合物具有较好的抗肿瘤活性,尤其是5-{6-[4-(2-羟基乙基)哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1,3,4-噻二唑-2-羧酸(2-甲氧基苯基)酰胺(8b)]和5-{6-[4-(2-羟基乙基)哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1,3,4-噻二唑-2-羧酸(4-甲氧基苯基)酰胺(8c)],对四种癌细胞都显示出较高的抗肿瘤活性,其抑制活性均优于阳性对照达沙替尼,随后对这类化合物抑制肿瘤的可能靶点开展了进一步研究.