Synthesis and Evaluation of Piperazine-Tethered Derivatives of Alepterolic Acid as Anticancer Agents

Alepterolic acid is a natural diterpenoid isolated from Aleuritopteris argentea with potential anti-cancer activity. In this study, alepterolic acid was modified to construct a series of arylformyl piperazinyl derivatives ( 3a – 3p ). The synthesized derivatives were fully characterized with HRMS, NMR, and IR. Four compounds with inhibition rate higher than 30 % at 10 μM ( 3f , 3n , 3g and 3k ) were further measured to obtain the IC₅₀ values against four cancer cell lines, including hepatoma cell lines HepG2, lung cancer cell lines A549, estrogen receptor-positive cell lines MCF7, and triple-negative breast cancer (TNBC) cell lines MDA-MB-231 by MTT assay. It was found that these compounds were more effective to HepG2 and MDA-MB-231 cells, while less toxic to A549 and MCF7 cells, and compound 3n as the most toxic derivatve against MDA-MB-231 cell lines, with IC₅₀ value of 5.55±0.56 μM. Trypan blue staining and colony formation assay showed that compound 3n inhibited the growth of MDA-MB-231 cells and prevented colony formation. Hoechst staining, flow cytometry and western blot analysis revealed that compound 3n induced caspase-dependent apoptosis in MDA-MB-231 cells. Conclusively, compound 3n was demonstrated to be a potential anti-cancer lead compound for further investigation.     

Synthesis and Evaluation of Novel Isoindoline-1,3-dione Derivatives as Anticancer Agents

Russian Journal of Bioorganic Chemistry - N-Substituted imides, isoindoline-1,3-dione derivatives, were synthesized, characterized, and investigated against blood cancer using K562 and Raji cell...     

Synthesis and Biological Evaluation of Matijin‐Su Derivatives as Potential Antihepatitis B Virus and Anticancer Agents

A series of Matijin‐Su (MTS, (2S)‐2‐{[(2S)‐2‐benzamido‐3‐phenylpropanoyl]amino}‐3‐phenylpropyl acetate) derivatives were synthesized and evaluated for their anti‐HBV and cytotoxic activities in vitro. Six compounds ( 4g , 4j , 5c , 5g , 5h and 5i ) showed significant inhibition against HBV DNA replication with the IC₅₀ values in range of 2.18 – 8.55 μm , which were much lower than that of positive control lamivudine (IC₅₀ 82.42 μm ). In particular, compounds 5h (IC₅₀ 2.18 μm ; SI 151.59) and 5j (IC₅₀ 5.65 μm ; SI 51.16) displayed relatively low cytotoxicities, resulting in high SI values. Notably, besides the anti‐HBV DNA replication activity, compound 4j also exhibited more potent in vitro cytotoxic activity than 5‐fluorouracil in two hepatocellular carcinoma cell (HCC) lines (QGY‐7701 and SMMC‐7721), indicating that 4j may be a promising lead for the exploration of drugs with dual therapeutic effects on HBV infection and HBV‐induced HCC.     

Synthesis and Cytotoxicity Screening of Some Synthesized Coumarin and Aza-Coumarin Derivatives as Anticancer Agents

Russian Journal of Bioorganic Chemistry - A series of coumarin and aza-coumarin derivatives (II–IX) were synthesized and identified using IR, 1H NMR, and 13C NMR spectral data. All the...     

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.     

Microwave-assisted Synthesis of Novel Thiazolocarbazoles and Evaluation as Potential Anticancer Agents. Part III

Novel 6-substituted thiazolocarbazole derivatives have been synthesized under microwave irradiation via the corresponding imino-1,2,3-dithiazoles. In vitro antitumor potential of these polyheterocyclic compounds was evaluated. Among all the tested thiazolocarbazoles, compound 10 is the most effective in inhibiting cell growth.     

Synthesis of Murrayaquinone-A Derivatives and Investigation of Potential Anticancer Properties

A series of novel murrayaquinone a derivatives were synthesized and their anti-cancer activity were evaluated on healthy colon cell lines (CCD-18Co), primary (Caco-2) and metastatic (DLD-1) colon cancer cell lines. The results showed that the cytotoxicity of murrayaquinone molecules is significantly high even in micromolar levels. The DNA binding, cell cycle arrest and metabolic activity studies of these molecules were also carried out and the results showed that these molecules induce apoptosis. In conclusion, the data support further studies on murrayaquinone derivatives toward selection of a candidate for cancer treatment.     

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Amide coupling reactions can be used to synthesize bispyridine-based ligands for use as bridging linkers in multinuclear platinum anticancer drugs. Isonicotinic acid, or its derivatives, are coupled to variable length diaminoalkane chains under an inert atmosphere in anhydrous DMF or DMSO with the use of a weak base, triethylamine, and a coupling agent, 1-propylphosphonic anhydride. The products precipitate from solution upon formation or can be precipitated by the addition of water. If desired, the ligands can be further purified by recrystallization from hot water. Dinuclear platinum complex synthesis using the bispyridine ligands is done in hot water using transplatin. The most informative of the chemical characterization techniques to determine the structure and gross purity of both the bispyridine ligands and the final platinum complexes is ¹H NMR with particular analysis of the aromatic region of the spectra (7-9 ppm). The platinum complexes have potential application as anticancer agents and the synthesis method can be modified to produce trinuclear and other multinuclear complexes with different hydrogen bonding functionality in the bridging ligand.     

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.     

Convenient Synthesis of Novel Chalcone and Pyrazoline Sulfonamide Derivatives as Potential Antibacterial Agents

Russian Journal of Bioorganic Chemistry - Novel chalcone sulfonamide derivatives were synthesized starting from benzophenones and aldehydes in 3 steps. Also,...     

6-Bromoquinazoline Derivatives as Potent Anticancer Agents: Synthesis,Cytotoxic Evaluation,and Computational Studies

A series of 6-bromoquinazoline derivatives ( 5a – j ) were synthesized. Cytotoxic effectiveness of compounds was done against two cancerous cell lines (MCF-7 and SW480) by standard MTT method. Fortunately, all of the compounds showed desirable activity in reducing the viability of the studied cancerous cell lines with IC₅₀ value in the range of 0.53–46.6 μM. Compound 5b with a fluoro substitution at meta position of the phenyl moiety showed stronger activity than cisplatin with IC₅₀=0.53–1.95 μM. Studies on the hit compound ( 5b ) through apoptosis assay illustrated that it could induce apoptosis in MCF-7 cell lines in dose dependent manner. Molecular docking study was done to investigate the detailed binding modes and interactions with EGFR as a plausible mechanism. The drug- likeness was predicted. To survey the reactivity of compounds, DFT calculation was performed. Taken together, 6-bromoquinazoline derivatives, especially 5b can be considered as hit compounds to rational drug designing as antiproliferative agents.     

C-Dimethylated Flavones as Possible Potential Anti-Tubercular and Anticancer Agents.

The present investigation describes an intramolecular Oxa-Michael addition of penta-substituted phenols to the enone of the tether in the presence of iodine as the oxidizing agent. Ten C-Dimethylated flavones with moderate to good yields ( 10a – j , 60–89 %) were isolated by heating the corresponding C-dimethylated chalcones using iodine in DMSO. Using the Microplate Alamar Blue test (MABA) technique, the drugs′ quantitative drug susceptibility against the H37Rv strain of replicating Mycobacterium TB was determined. The sensitivity of two of the developed compounds ( 10e , 10h ) was up to 6.25 g/mL. The human lung adenocarcinoma cell lines (A549) were used in the anticancer study, which was carried out using the MTT cell proliferation assay. In A549 cell lines, four flavones demonstrated anticancer activity with IC₅₀ values between 39 and 48 μM. The C-dimethylated flavones, 10b (3,4-dimethoxy), 10c (2,3,4-trimethoxy), 10e (p-fluoro) and 10 g (N-methyl indole) substitutions on ring ‘B’ showed good anticancer activity with IC₅₀ values 39.17, 39.21, 48.43 and 43.48 μM, respectively. The compounds 10b , 10c , 10d , 10e , and 10i had improved binding and interaction profiles among all the compounds examined during the current In Silico research, as shown by the docking simulations against two targets EGFR and MTB MurI.     

The Synthesis of Derivatives of 2-Arylamino ara-Carbocyclic Purine Nucleosides as Potential Anti-Viral Agents

Abstract

A general synthetic method into 2-arylamino ara-carbocyclic purine nucleosides from 2,4,6-mchloropyrimidine is described.     

Venom-Derived Bioactive Compounds as Potential Anticancer Agents: A Review

International Journal of Peptide Research and Therapeutics - Biologically active compounds with potential anticancer activity have been isolated from various animal sources. Recent research is...     

Synthesis,Molecular Modeling,and Biological Evaluation of Novel Chiral Thiosemicarbazone Derivatives as Potent Anticancer Agents

A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF‐7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC‐27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound 17b exhibited the most potent activity (IC₅₀ 4.6 μM) against HGC‐27 as compared with the reference compound, sindaxel (IC₅₀ 10.3 μM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents. Chirality 27:177–188, 2015. © 2014 Wiley Periodicals, Inc.     

Design,Synthesis, Cytotoxic Screening and Molecular Docking Studies of Novel Hybrid Thiosemicarbazone Derivatives as Anticancer Agents

Thiosemicarbazones have been the focus of scientists owing to their broad clinical anticancer range. Herein, A Series of new thiosemicarbazone derivatives 5 – 9 were synthesized and confirmed through the use of different spectroscopic techniques along with elemental analysis. The in vitro cytotoxic activity of compounds 5 – 9 against MCF-7 and A549 cell lines and normal breast cells were assessed. Several compounds were found to be active. The most active compound 7 caused MCF-7 cell cycle arrest at G1/ S phases; and induced apoptosis at the pre-G1 phase. The apoptosis-inducing activity of compound 7 was proofed by the elevation of caspase 3/7 activity and also by up-regulation of the expression of Bax and p53 proteins together with the down-regulation of the expression of the Bcl-2 protein. It also had a strong inhibitory effect topoisomerase IIβ enzyme. Molecular Docking study revealed that the synthesized compounds had good docking scores compared to the standard drug Etoposide towards the topoisomerase IIβ protein (3QX3). Overall, these findings confirmed that the new thiosemicarbazone derivatives could aid in the development of promising cancer drug candidates.     

Synthesis of Ester-Linked Ursolic Acid-Based Hybrid Compounds: Potential Antibacterial and Anticancer Agents

The molecular hybridization of two or more drugs into a single molecule is an effective drug design approach to reduce pill burden and improve patient treatment adherence. Ursolic acid-based hybrid compounds were synthesized and characterized followed by molecular docking studies. In vitro studies against various bacterial strains and human cancer cells (MDA-MB-231, HeLa, and MCF-7) were performed. Compounds 14 – 19 , 21 , 34 , 31 , and 30 demonstrated significant antibacterial activities with MIC values of 15.625 μg/ml. Compounds 29 and 34 were more cytotoxic than ursolic acid, with IC₅₀ values of 46.99 and 48.18 μg/ml. Compounds 29 and 34 in the docking studies presented favourable binding interactions and better docking energy against the Epidermal Growth Factor Receptor (EGFR) than the parent compound, ursolic acid. The findings revealed that the ursolic acid scaffold is a promising precursor for the development of molecules with promising anticancer and antimicrobial activities. However, more studies are needed to fully understand their mode of action.     

Synthesis and Biological Evaluation of Novel Gigantol Derivatives as Potential Agents in Prevention of Diabetic Cataract

As a continuation of our efforts directed towards the development of natural anti-diabetic cataract agents, gigantol was isolated from Herba dendrobii and was found to inhibit both aldose reductase (AR) and inducible nitric oxide synthase (iNOS) activity, which play a significant role in the development and progression of diabetic cataracts. To improve its bioefficacy and facilitate use as a therapeutic agent, gigantol (compound 14f) and a series of novel analogs were designed and synthesized. Analogs were formulated to have different substituents on the phenyl ring (compounds 4, 5, 8, 14a-e), substitute the phenyl ring with a larger steric hindrance ring (compounds 10, 17c) or modify the carbon chain (compounds 17a, 17b, 21, 23, 25). All of the analogs were tested for their effect on AR and iNOS activities and on D-galactose-induced apoptosis in cultured human lens epithelial cells. Compounds 5, 10, 14a, 14b, 14d, 14e, 14f, 17b, 17c, 23, and 25 inhibited AR activity, with IC₅₀ values ranging from 5.02 to 288.8 μM. Compounds 5, 10, 14b, and 14f inhibited iNOS activity with IC₅₀ ranging from 432.6 to 1188.7 μM. Compounds 5, 8, 10, 14b, 14f, and 17c protected the cells from D-galactose induced apoptosis with viability ranging from 55.2 to 76.26%. Of gigantol and its analogs, compound 10 showed the greatest bioefficacy and is warranted to be developed as a therapeutic agent for diabetic cataracts.