Anticancer Activity Of Compounds Research Articles

Discovering Dually Active Anti-cancer Compounds with a Hybrid AI-structure-based Approach.

Cancer's persistent growth often relies on its ability to maintain telomere length and tolerate the accumulation of DNA damage. This study explores a computational approach to identify compounds that can simultaneously target both G-quadruplex (G4) structures and poly(ADP-ribose) polymerase (PARP)1 enzyme, offering a potential multipronged attack on cancer cells. We employed a hybrid virtual screening (VS) protocol, combining the power of machine learning with traditional structure-based methods. PyRMD, our AI-powered tool, was first used to analyze vast chemical libraries and to identify potential PARP1 inhibitors based on known bioactivity data. Subsequently, a structure-based VS approach selected compounds from these identified inhibitors for their G4 stabilization potential. This two-step process yielded 50 promising candidates, which were then experimentally validated for their ability to inhibit PARP1 and stabilize G4 structures. Ultimately, four lead compounds emerged as promising candidates with the desired dual activity and demonstrated antiproliferative effects against specific cancer cell lines. This study highlights the potential of combining Artificial Intelligence and structure-based methods for the discovery of multitarget anticancer compounds, offering a valuable approach for future drug development efforts.

Synthesis and anticancer evaluation of diaryl pyrido[2,3-d]pyrimidine /alkyl substituted pyrido[2,3-d]pyrimidine derivatives as thymidylate synthase inhibitors

Worldwide, colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related deaths. Thymidylate synthase (TS) is a crucial component of DNA biosynthesis and has drawn interest as an essential target for cancer treatment. In the current work, we have designed and synthesized twenty-eight new diaryl-based pyrido[2,3-d]pyrimidine/alkyl-substituted pyrido[2,3-d]pyrimidine derivatives and evaluated their anticancer activity against the HCT 116, MCF-7, Hep G2, and PC-3 cell lines cell lines. Additionally, we have carried out TS inhibitory activity and in silico studies for compounds 1n and 2j. All the synthesized compounds exhibited good anticancer activity, but among them, compounds 1n and 2j showed excellent anticancer activity, having IC50 values of 1.98 ± 0.69, 2.18 ± 0.93, 4.04 ± 1.06, and 4.18 ± 1.87 µM; and 1.48 ± 0.86, 3.18 ± 0.79, 3.44 ± 1.51, and 5.18 ± 1.85 µM, against the HCT 116, MCF-7, Hep G2, and PC-3 cell lines respectively with control raltitrexed (IC50 1.07 ± 1.08, 1.98 ± 0.72, 1.34 ± 1.0, and 3.09 ± 0.96 µM, respectively) and hTS inhibitory activity with IC50 values of 20.47 ± 1.09 and 13.48 ± 0.96 nM with control raltitrexed (IC50 14.95 ± 1.01 nM). Further, the mechanism of inhibition was revealed by molecular docking, which showed the binding pattern of 1n and 2j to the catalytic site of TS with docking scores of -10.6 and − 9.5 kcal/mol, respectively, with reference raltitrexed (-9.4 kcal/mol). Additionally, the assessment of physicochemical, biochemical, structural, and toxicological characteristics were also in the acceptable range for these compounds. Based on the anticancer activity of compounds, SAR was also performed for lead optimization.

Multitask Learning on Graph Convolutional Residual Neural Networks for Screening of Multitarget Anticancer Compounds.

Recently, various modern experimental screening pipelines and assays have been developed to find promising anticancer drug candidates. However, it is time-consuming and almost infeasible to screen an immense number of compounds for anticancer activity via experimental approaches. To partially address this issue, several computational advances have been proposed. In this study, we present iACP-GCR, a model based on multitask learning on graph convolutional residual neural networks with two types of shortcut connections, to identify multitarget anticancer compounds. In our architecture, the graph convolutional residual neural networks are shared by all the prediction tasks before being separately customized. The NCI-60 data set, one of the most reliable and well-known sources of experimentally verified compounds, was used to develop our model. From that data set, we collected and refined data about compounds screened across nine cancer types (panels), including breast, central nervous system, colon, leukemia, nonsmall cell lung, melanoma, ovarian, prostate, and renal, for model training and evaluation. The model performance evaluated on an independent test set shows that iACP-GCR surpasses the three advanced computational methods for multitask learning. The integration of two shortcut connection types in the shared networks also improves the prediction efficiency. We also deployed the model as a public web server to assist the research community in screening potential anticancer compounds.

Inhibitory capacity of xanthine oxidase, and anticancer activity of compounds from Sarcandra glabra (Thunb.) Nakai flower

The flower of Sarcandra glabra (Thunb.) Nakai (FSN) has been considered an important supplementation material in natural flower-flavoured tea products in Vietnam. The present work has considerable significance for adding pharmacological value of FSN. Two compounds, namely emodin and methyl rosmarinate, were identified for the first time from a methanolic extract of FSN from Vietnam while analysing the inhibitory capacity of xanthine oxidase and cytotoxic activities. High levels of xanthine oxidase inhibiting capacity and cytotoxicity activity against HepG2 and A549 cancer cell lines were detected from emodin, with IC50 of 4.88 ± 0.42, 13.72 ± 0.48, and 18.33 ± 0.10 µg/mL, respectively. Emodin also activated the apoptotic factors of caspase-9, Bax, and PARP in HepG2, and caspase-3/9 and p53 in A549. Our results revealed for the first time the xanthine oxidase inhibitory effect of M70 with IC50 of 34.15 ± 1.33 µg/mL, which would shed light on its potential application for developing anti-hyperuricemia agents. The present work suggested that using flower-flavoured tea product of FSN could have many health benefits for gout patients.

Anthriscus sylvestris: An overview on Bioactive Compounds and Anticancer Mechanisms from a Traditional Medicinal Plant to Modern Investigation.

Anthriscus sylvestris (L.) Hoffm. Gen. is a biennial or perennial herb commonly found in China. It has a long history of use in traditional Chinese medicine to treat various ailments such as cough, gastric disorders, spleen deficiency, and limb weakness. Recently, its potential as an anticancer agent has gained considerable attention and has been the subject of extensive research focusing on extract efficacy, identification of active compounds, and proposed molecular mechanisms. Nevertheless, further high-quality research is still required to fully evaluate its potential as an anticancer drug. This review aims to comprehensively summarize the anticancer properties exhibited by the active components found in Anthriscus sylvestris. We conducted a comprehensive search, collation, and analysis of published articles on anticancer activity and active compounds of A. sylvestris using various databases that include, but are not limited to, PubMed, Web of Science, Science Direct and Google Scholar. The primary chemical composition of A. sylvestris consists of phenylpropanoids, flavonoids, steroids, fatty acids, and organic acids, showcasing an array of pharmacological activities like anticancer, antioxidant, anti-aging, and immunoregulatory properties. Thus, this review highlights the active compounds isolated from A. sylvestris extracts, which provide potential leads for the development of novel anticancer drugs and a better understanding of the plant's pharmacological effects, particularly its anticancer mechanism of action.

Anticancer Potential of the S-Heterocyclic Ring Containing Drugs and its Bioactivation to Reactive Metabolites.

Sulfur-containing heterocyclic derivatives have been disclosed for binding with a wide range of cancer-specific protein targets. Various interesting derivatives of sulfur-containing heterocyclics such as benzothiazole, thiazole, thiophene, thiazolidinedione, benzothiophene, and phenothiazine, etc have been shown to inhibit diverse signaling pathways implicated in cancer. Significant progress has also been made in molecular targeted therapy against specific enzymes such as kinase receptors due to potential binding interactions inside the ATP pocket. Sulfur-containing heterocyclic ring metal complexes i. e., benzothiazole, thiazole, thiophene, benzothiophene and phenothiazines are among the most promising active anticancer compounds. However, sulfur heteroaromatic rings, particularly thiophene, are of high structural alert due to their metabolism to reactive metabolites. The mere presence of a structural alert itself does not determine compound toxicity therefore, this review focuses on some specific findings that shed light on factors influencing the toxicity. In the current review, synthetic strategies of introducing the sulfur core ring in the synthesized derivatives are discussed with their structure-activity relationships to enhance our understanding of toxicity mechanisms and develop safer therapeutic options. The sulfur-containing marketed anticancer drugs included in this review direct the synthesis of novel compounds and will help in the development of potent, safer sulfur-based anticancer drugs in near future.

Marine algae-derived characterized bioactive compounds as therapy for cancer: A review on their classification, mechanism of action, and future perspectives.

In 2022, there were around 20 million new cases and over 9.7 million cancer-related deaths worldwide. An increasing number of metabolites with anticancer activity in algae had been isolated and identified, which were promising candidates for cancer therapy. Red algae are well-known for the production of brominated metabolites, including terpenoids and phenols, which have the capacity to induce cell toxicity. Some non-toxic biological macromolecules, including polysaccharides, are distinct secondary metabolites found in many algae, particularly green algae. They possess anticancer activities by inhibiting tumor angiogenesis, stimulating the immune response, and inducing apoptosis. However, the structure-activity relationship between these components and antitumor activity, as well as certain taxa within the algae, remains relatively unstudied. This work is based on the reports published from 2003 to 2024 in PubMed and ISI Web of Science databases. A comprehensive review of the characterized algal anticancer active compounds, together with their structure and mechanism of action was performed. Also, their structure-activity relationship was preliminarily summarized to better assess their potential properties as a natural, safe bioactive product to be used as an alternative for the treatment of cancers, leading to new opportunities for drug discovery.

2‐(1‐Methyl‐1H‐indazol‐5‐yl)‐N‐arylisonicotinamide Analogs: Synthesis, Anticancer Screening, SAR and ADMET Studies

AbstractIn this current research framework, we detailed the synthesis of ten novel 2‐(1‐methyl‐1H‐indazol‐5‐yl)‐N‐arylisonicotinamide analogs (3a–j). The synthesis of these compounds (3a–j) involved a three‐step process, employing the Suzuki‐Miyaura coupling reaction, which successfully linked 1‐methyl‐1H‐indazole with isonicotinamide to satisfactory yields. The synthesized compounds were characterized using various spectroscopic techniques. To assess their potential, the anticancer activity of compounds (3a–j) was evaluated following the National Cancer Institute (NCI US) protocol against nine panels comprising different cancer cell lines, at a concentration of 10−5 M. Growth percentage (GP) and percentage growth inhibition (PGI) were calculated for each compound. Notably, the CNS cancer cell line SNB‐75 exhibited a remarkable PGI of 99.16 percent, indicating high sensitivity to the tested compound 3e. Additionally, ADMET prediction suggested that most of the synthesized compounds possess drug‐like properties, with low adverse effects and toxicity. These findings represent a significant advancement, offering potential avenues for further developments in the field of cancer research.

Abstract 1817: Association of nuclear morphometrical variables with drug cytotoxicity: A proof of principle using NCI-60 anti-cancer drug screening panel

Abstract The National Cancer Institute’s panel of 60 cancer cell lines (NCI-60) have been extensively used to screen compounds for anti-cancer activity in a wide range of molecular and pharmacologic assays. We completed a detailed analysis of the nuclear morphometric variables of 57 cancer cell lines from this drug-discovery panel using recently developed computerized method that allows simultaneously assess 42 variables related to morphology/texture of the cell nuclei. The goal of this study was to determine whether unique nuclear patterns seen in cancer cells can effectively predict response to anti-cancer therapies. Stained sections prepared from paraffin cell blocks were used to measure each cell nucleus by size (e.g. area, perimeters); by shape (e.g. area box, fractal dimensions, roundness); and by optical density of the pixels and texture (e.g. margination, heterogeneity). The obtained values were then summarized at the cell line level, generating a dataset comprising 84 variables, represented by mean values and coefficients of variation. We filtered the complete set of chemical compounds, tested on the NCI-60 panel, based on sufficient GI50 variability, narrowing the list down to 4,839 compounds. These compounds were further refined using the Benjamini-Hochberg false discovery rate (FDR) method at 1% FDR, based on the p-values from “goodness of fit” tests. This process identified 1,314 compounds where the inclusion of morphometric variables significantly improved the fit of our models. To determine which variables were highly predictive for GI50 in each compound, we performed lasso regression per compound of logged GI50 versus dummied tissue of origin and morphometric variables. We tabulated the proportion of compound models selecting each variable as well as the median relative strength for each variable. This procedure identified 10 promising compound models, in which the top 5 values of relative strength from each of the tested variables emerged. Our primary objective in this analysis was to find associations between certain nuclear morphometric parameters of tumors cells and drug sensitivity. Better defining how to use these previously untapped clues may pave the way for future studies able to predict sensitivity to cancer drugs and to help in the selection of the best anticancer treatments. Additionally, our work may draw new attention to compounds not now used for anticancer treatments, but whose increased cytotoxicity can be linked to abnormal morphometric parameters that indicate possible anti-tumor activity. Citation Format: Geula Klorin, Luz María Rodríguez, Edmond Sabo, Grant Izmirlian, Amnon Amit, Paul Meltzer, Anna Roschke. Association of nuclear morphometrical variables with drug cytotoxicity: A proof of principle using NCI-60 anti-cancer drug screening panel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1817.

Abstract 2186: Bacterial lung cancer therapeutics from soil bacteria in New York City

Abstract The microbiome's diverse functions in human health have generated increasing interest in using live bacteria for cancer therapy. Due to their natural presence in colon, lung and breast tissue, bacterial therapies have been augmented using synthetic biology in order to treat infections, inflammation, and cancer. One major challenge is finding safe and effective host species and therapeutic payloads for a particular type of cancer. Here we explored the vast diversity of microbial isolates in the environment as a valuable source of novel therapeutic compounds that can be expressed by bacteria. Specifically, we isolated and identified soil bacteria from 25 local parks, and investigated their secreted compounds for anti-cancer activity using monolayer and 3D-spheroid cultures of lung cancer. Through metagenomic analysis, toxicology assays, varied growth conditions, and bacteria-cancer co-culture experiments, we found Bacillus spp. isolates from Manhattan parks' soil that secreted products with high, dose-dependent cytotoxicity against lung cancer models. We also demonstrate that Bacillus subtilis, a model organism for gram-positive bacteria, can colonize lung cancer tumor spheroids, pointing to its use as a viable strain for bacteria cancer therapy. The work presented here underscores the potential of harnessing environmental microbial diversity for the development of gram positive species and their compounds as cancer therapeutics. Citation Format: Dhruba Deb, Tal Danino. Bacterial lung cancer therapeutics from soil bacteria in New York City [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2186.

Synthesis of magnetic bifunctional monomer molecularly imprinted polymers for highly selective separation of paclitaxel from Taxus cuspidata

Paclitaxel (PTX), an active anticancer compound derived from Taxus cuspidata, possesses considerable economic value. Given the abundance of structural analogs, the selective separation of PTX from T. cuspidata presents a formidable challenge. In this study, the bifunctional monomers magnetic molecular imprinted polymers (MMIPs) with multiple active sites were synthesized using Fe3O4 as the magnetic carrier, PTX as the template, 4-vinylpyridine (4-VP) and methacrylic acid (MAA) as the first-stage and the second-stage pre-assembly functional monomer, respectively. The results indicated that MMIPs exhibited excellent magnetic recovery capability and high adsorption capacity for PTX. Furthermore, the adsorption behaviors were more consistent with Langmuir isotherm model and pseudo-second-order kinetic model. The MMIPs possessed significantly higher selectivity for PTX than five structural analogs (Docetaxel, Baccatin III, 10-Deacetylbaccatin III, and Glucose) and recyclability for up to six cycles. Additionally, the adsorption mechanism analysis indicated that the excellent performance of MMIPs primarily arises from the multiple active binding sites involving hydrogen bonding and π-π stacking. Finally, MMIPs were used for PTX recognition and separation in T. cuspidata extracts. This study provides an efficient method and valuable theoretical basis for the highly selective separation of PTX from T. cuspidata.

Identification of cancer inhibitors from Hystrix brachyurabezoar extracts using LC-MS multivariate data analysis and in silico evaluation on Bcl-2, cyclin B/CDK1, VEGF and NM23-H1

Hystrix brachyurabezoar is calcified undigested material found in the gastrointestinal tract known for various medicinal benefits including as an anticancer agent. However, the H. brachyurapopulation has been declining due to its demand and is under Malaysian law protection. Therefore, present study aimed to identify bezoar anticancer active compounds through metabolomics and in-silico approaches. Five replicates of bezoar powder were subjected to extraction using different solvent ratios of methanol-water (100, 75, 50, 25, 0% v/v). Cytotoxicity and metabolite profiling using liquid chromatography-mass spectrometry were conducted. Putative compounds identified were subjected to in-silico analysis with targeted anticancer proteins namely, Bcl-2, Cyclin B/CDK1 complex, VEGF and NM23-H1. The correlation of LC-MS and cytotoxicity profile pinpointed two compounds, mangiferin and propafenone. In-silicostudy showed both compounds exerted good binding scores to all proteins with hydrophobic interaction dominating the ligand-protein complex binding, suggesting the ligands act as hydrophobes in the interactions.

Isolation of active compounds from Streptomyces sennicomposti GMY01 and cytotoxic activity on breast cancer cells line

The occurrence of resistance to anticancer and the emergence of serious side effects due to chemotherapy is one of the main problems in cancer treatment, including breast cancer. The need for effective anticancer with a specific target is urgently required. Streptomyces are widely known as the potential producers of new anticancer molecules. Previously reported that the methanol extract of Streptomyces sennicomposti GMY01 isolated from Krakal Coast, Gunungkidul had very strong cytotoxic activity against MCF-7 and T47D breast cancer cells with IC50 values of 0.6 and 1.3 μg/mL, respectively. The following study aimed to isolate and identify active compounds of the S. sennicomposti GMY01 and evaluate its cytotoxic activity. The study was started by re-culturing and re-fermented optimization of S. sennicomposti GMY01 in a larger volume, then the bacteria were extracted using methanol following the bioassay-guided isolation of the extract obtained. The active compounds obtained were then structurally determined using UV/Vis spectroscopy, Fourier Transform-Infrared (FT-IR), Liquid Chromatography-Mass Spectroscopy (LC-MS), 1H NMR, and 13C NMR and analyzed for their cytotoxic activity using MTT assay on MCF-7 and normal Vero cells line. The results showed that the culture of the S. sennicomposti GMY01 using Starch Nitrate Broth (SNB) media yields the best results compared to other culture media. An active anticancer compound namely mannotriose was successfully isolated from the methanol extract with an IC50 value of 5.6 μg/mL and 687 μg/mL against the MCF-7 and Vero cells lines, respectively, indicating that this compound showed strong cytotoxic activity with high selectivity.

COMPUTATIONAL STUDIES AND GREEN SYNTHESIS OF BENZIMIDAZOLES THROUGH SEQUENTIAL OXIDATIVE CYCLISATION OF ARYLDIAMINES IN SOLVENT-FREE CONDITIONS

Benzimidazoles were synthesized under solvent-free conditions using Ionic Liquids (IL), specifically 1-Pentyl-3- methylimidazolium bromide ([pmim]Br), derived from aryl aldehydes and phenylenediamine. A comparative study of yields was conducted by reacting aryl aldehydes with both electron-donating and electron-withdrawing groups with substituted o-phenylenediamines, resulting in the formation of 2-phenylbenzimidazoles via cyclization. The yield of final products, optimum reaction conditions, plausible mechanism of the reaction, and the effect of substitutions at various positions of either of the reactants are presented in this paper. Computational studies have been done to explore the possibility of synthesized compounds for anticancer activity. Molecular docking studies were conducted to explore the inhibitory effects of steroidal derivatives against the estrogen receptor-derived Mutants [PDB ID: 2ITO]. The docking results of all compounds revealed significant inhibitory activity against the estrogen receptor 2ITO, with binding energy (ΔG) values for compounds 3a, 3b, 3c, 3d, 3e, 3f, and 3g against protein 2ITO recorded as -7.1 Kcal/mole, -7.3 Kcal/mole, -7.2 Kcal/mole, -7.8 Kcal/mole, -7.5 Kcal/mole, -7.6 Kcal/mole, and -7.6 Kcal/mole respectively.

New thiophene-1,3,4-oxadiazole-thiazolidine-2,4-dione hybrids: Synthesis, MCF-7 inhibition and binding studies

Two synthetic methods were proposed for the preparation of a new series of thiophene-1,3,4-oxadiazole-thiazolidine-2,4-dione hybrids (TOT-1 to 15) and their structures were elucidated based on spectral data. Studies on cytotoxicity, ROS, cellular uptake and interactions of TOT-14 with calf thymus DNA were carried out. Anticancer activity of compounds, TOT-1 to 15 on breast cancer (MCF-7) cell lines was investigated. The IC50 values for the standard, epirubicin hydrochloride and TOT-12, 13, 14 and 15 were found to be 6.78, 5.52, 6.53, 4.83 and 5.57 µg/mL, respectively. Notably, TOT-14 exhibited a remarkable antiproliferative activity with a strikingly selective inhibitory effect compared to standard. This specific selectivity could be attributed to the synergistic effect of increased cellular uptake and generation of higher ROS in cancer cells after irradiation. The binding constant of 4.25 x 103 M−1 indicated the moderate interaction between TOT-14 and ct-DNA. The docking score of TOT derivativeswas substantially identical to the docking score of epirubicin hydrochloride. The designed molecules complied with the requirements for drug-likeness and ADME.

Synthesis and Investigation of Cytotoxicity in Different Cell Lines of Novel Hydroxypyranones

Mannich bases synthesized from kojic acid have been determined in extensive studies conducted by our study group that they have a wide variety of biological activities. 
 In this study, new anticancer-active compounds were synthesized from compounds with high anticancer activity. The compounds' structures were identified through the utilization of spectroscopic methods and elemental analyses. The cytotoxicity screening of the compounds were done by MTT assay on different human cancer cell lines.
 Compound 1 bearing iodomethyl moiety, showed remarkable cytotoxicity with IC50 values in the range of 8.11 and 21.24 µg/mL. The IC50 value on Vero (African green monkey kidney epithelial) is over 100 µg/mL which means low cytotoxicity against healthy cells. Compared to this, SK-MEL cells have 12 times less IC50 value, with a therapeutic index over 12. The closest cytotoxic effectivity to KOJI MG84 which is previously reported as a cytotoxic agent, is observed on the SK-MEL cell line in compound 1, with 4 times less cytotoxic activity.

Rational design and eco-friendly one-pot multicomponent synthesis of novel ethylidenehydrazineylthiazol-4(5H)-ones as potential apoptotic inducers targeting wild and mutant EGFR-TK in triple negative breast cancer

A novel series of ethylidenehydrazineylthiazol-4(5H)-ones were synthesized using various eco-friendly one-pot multicomponent synthetic techniques. The anticancer activity of compounds (4a-m) was tested against 11 cancer cell lines. While the IC50 of all compounds was evaluated against the most sensitive cell lines (MDA-MB-468 and FaDu). Our SAR study pinpointed that compound 4a, having a phenyl substituent, exhibited a significant growth inhibition % against all cancer cell lines. The frontier anticancer candidates against the MDA-MB-468 were also examined against the wild EGFR (EGFR-WT) and mutant EGFR (EGFR-T790M) receptors. Most of the synthesized compounds exhibited a higher inhibitory potential against EGFR-T790M than the wild type of EGFR. Remarkably, compound 4k exhibited the highest inhibitory activity against both EGFR-WT and EGFR-T790M with IC50 values (0.051 and 0.021 µM), respectively. The pro-apoptotic protein markers (p53, BAX, caspase 3, caspase 6, caspase 8, and caspase 9) and the anti-apoptotic key marker (BCL-2) were also measured to propose a mechanism of action for the compound 4k as an apoptotic inducer for MDA-MB-468. Investigation of the cell cycle arrest potential of compound 4k was also conducted on MDA-MB-468 cancer cells. We also evaluated the inhibitory activities of compounds (4a-m) against both EGFR-WT and EGFR-T790M using two different molecular docking processes.

Synthesis, Antiproliferative Activity and In Silico Studies of Chalcones Derived From 4-(Imidazole-1-yl)Acetophenone

In this study, the synthesis of chalcone compounds (1-11) derived from 4-(imidazol-1-yl)acetophenone and the structure determination of these compounds by various spectroscopic methods were carried out. The anticancer activities of compounds 1-11 were examined against HeLa and PC-3 cancer cells at four different concentrations (100, 50, 25, and 5 µM) using the BrdU ELISA assay. It was determined that all molecules except compounds 1 and 6 in HeLa cancer cells and compounds 2 and 8 against PC-3 cancer cells were more active against HeLa and PC-3 than the standard drug 5-fluorouracil (5-FU). The best activity against PC-3 cancer cells was compound 4 (IC50: 1.39±0.00 µM). In addition, compound 11 (IC50: 1.58±0.01 µM) was found to have the highest activity against HeLa cancer cells. Compound 4 against PC-3 cancer cell and compound 11 against HeLa cancer cell displayed cell selective activity. The ADME properties and drug similarities of the molecules 1-11 using the SwissADME software were investigated. According to these properties, compounds 1-11 were found to obey Lipinski rules.

Development of nanofunctionalized oxovanadium(IV) complex and its anticancer, antidiabetic, DNA cleavage and cell imaging studies

VO(IV) complex is little toxic and highly effective than vanadium salts. A vanadyl metal complex from 8-formyl-7-hydroxy-4-methyl coumarin derivative has been synthesized and functionalized with copper nanoparticles. The Spectrochemical studies such as UV, FTIR, 1NMR and ESR spectra were recorded to characterize the ligand(CUAP), Vanadyl complex[VO(CUAP)SO4] and nano Cu-VO(IV)complex efficiently. The structural studies of vanadyl complex confirmed that the ligand coordinate with metal through nitrogen atom of azomethine, carbonyl oxygen and phenolic oxygen. ESR spectrum of vanadyl complex revealed the covalent nature. XRD pattern of nano Cu-VO(IV) complex indicated the crystalline nature and the average particle size was 20.91 nm. SEM image of nano Cu-VO(IV) complex showed that the nano particles accumulated to form spherical shaped particles. The particle size obtained from Transmission Electron Microscopy of nano functionalized metal complex is ∼ 20 nm. It is closely matched to the particle size calculated from XRD results. Fluorescence of vanadyl complex and nano Cu-VO(IV) complex exhibit the emission from 270 to 900 nm range with significant fluorescence at ∼ 750 nm. The DNA cleavage of all the compounds was evaluated using Agarose gel electrophoresis technique and showed greater cleavage of vanadyl complex. The anticancer activity of compounds was carried out against two cancer cell lines viz Human Breast Cancer Cell line (MCF-7) and Human Leukemia Cancer Cell Line(K-562). Oxovanadium complex exhibited good anticancer activities than ligand and nano-functionalized complex. The antidiabetic activities of vanadyl and nano functionalized complexes were studied against α-Amylase and β-Glucosidase inhibition assay. In this study vanadyl complex showed higher inhibition activity on α-Amylase compared with standard Acarbose. The bioimaging of nano-functionalized metal complex showed high fluorescent properties. The molecular docking study of ligand and vanadyl complex showed greater docking results with CDK2 receptor.

Evaluation of cytotoxic activity of Syringodium isoetifolium against human breast cancer cell line - an in silico and in vitro study

Seagrass is a natural, renewable, and much unexplored marine resource, which are capable, and reliable sources in the field of pharmaceuticals and drug discovery. The seagrass, Syringodium isoetifolium is our target plant for the study, which was collected from the Ramanathapuram district, Tamil Nadu.The current study is focused to evaluate the cytotoxic, cell cycle arrest, and apoptotic induction activities of the hydroalcoholic extract of S. isoetifolium against the human breast cancer (MCF-7) cell line. The cytotoxic evaluation revealed that the extract inhibited MCF-7 proliferation with IC50 value of 230.32 μg/ml. Evaluation of MCF-7 cell cycles demonstrated that the extract arrested the cell cycle in the S phase and continued to the G2/M phase at half of the IC50 value. The extract induced apoptotic of MCF-7 cells about 30.61% which was nearly the same with aripiprazole as a positive control (52.35%). Nootkatone significantly binds to the target proteins – HSP 90 and HER2 kinase with the least binding energy was predicted as the most active anticancer compounds by a molecular docking study. In light of the findings, it can be said that the hydroalcoholic extract of S. isoetifolium has the potential to be a therapeutic agent for breast malignancies by acting as an anticancer component. It can be used as an anticancer agent on its own and/or as a scaffold for analog synthesis to develop novel anticancer agents with improved therapeutic efficacy.