Prospective Anticancer Agents Research Articles

Synthesis and SAR investigation of biphenylaminoquinoline derivatives with benzyloxy substituents as promising anticancer agents.

The biphenyl scaffold represents a prominent privileged structure within the realms of organic chemistry and drug development. Biphenyl derivatives have demonstrated notable biological activities, including antimicrobial, anti-inflammatory, anti-HIV, and the treatment of neuropathic pain. Importantly, their anticancer abilities should not be underestimated. In this context, the present study involves the design and synthesis of a series of biphenyl derivatives featuring an additional privileged structure, namely the quinoline core. We have also diversified the substituents attached to the benzyloxy group at either the meta or para position of the biphenyl ring categorized into two distinct groups: [4,3']biphenylaminoquinoline-substituted and [3,3']biphenylaminoquinoline-substituted compounds. We embarked on an assessment of the cytotoxic activities of these derivatives in colorectal cancer cell line SW480 and prostate cancer cell line DU145 for exploring the structure-activity relationship. Furthermore, we determined the IC50 values of selected compounds that exhibited superior inhibitory effects on cell viability against SW480, DU145 cells, as well as MDA-MB-231 and MiaPaCa-2 cells. Notably, [3,3']biphenylaminoquinoline derivative 7j displayed the most potent cytotoxicity against these four cancer cell lines, SW480, DU145, MDA-MB-231, and MiaPaCa-2, with IC50 values of 1.05 μM, 0.98 μM, 0.38 μM, and 0.17 μM, respectively. This highly promising outcome underscores the potential of [3,3']biphenylaminoquinoline 7j for further investigation as a prospective anticancer agent in future research endeavors.

Gold(Ⅰ) organometallics with alkynyl and N-heterocyclic carbene ligands and their medicinal and computational chemistry evaluation as prospective anticancer drugs

Gold(Ⅰ) organometallics of the type alkynylgold(Ⅰ)(NHC) (where NHC = N-heterocyclic carbene) 5a – 5f and 6a/b were prepared and evaluated as prospective anticancer agents by computational and medicinal chemistry methods. DFT calculations showed similar stability for the series, with differing dipole moments, depending on the substituents on the alkynyl and the NHC ligands. Studies in cancer cell lines indicated in general that the complexes with the largest dipole moments exhibited the highest antiproliferative activity in comparison with structurally closely related complexes. Thus, complexes 5f, (with 4-fluoroethynylbenzene as alkynyl precursor), and 6b, (with mestranol as alkynyl precursor) containing the same methoxy‑substituted NHC ligand showed in general the strongest biological activity. Protein binding studies confirmed a high affinity to albumin (around 90 %) and cellular uptake studies indicated an increased uptake of the most active complex 5f.

Exploring the Anticancer Potential of Semisynthetic Derivatives of 7α-Acetoxy-6β-hydroxyroyleanone from Plectranthus sp.: An In Silico Approach.

The diterpene 7α-acetoxy-6β-hydroxyroyleanone isolated from Plectranthus grandidentatus demonstrates promising antibacterial, anti-inflammatory and anticancer properties. However, its bioactivity may be enhanced via strategic structural modifications of such natural products through semisynthesis. The anticancer potential of 7α-acetoxy-6β-hydroxyroyleanone and five derivatives was analyzed in silico via the prediction of chemicals absorption, distribution, metabolism, excretion, and toxicity (ADMET), quantum mechanical calculations, molecular docking and molecular dynamic simulation. The protein targets included regulators of apoptosis and cell proliferation. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Derivatives 7α-acetoxy-6β-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6β-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone achieved high predicted binding affinities towards their respective protein panels, with stable molecular dynamics trajectories. Both compounds demonstrated favorable ADMET parameters and toxicity profiles. Their stability and reactivity were confirmed via geometry optimization. Network analysis revealed their involvement in cancer-related pathways. Our findings justify the inclusion of 7α-acetoxy-6β-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6β-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone in in vitro analyses as prospective anticancer agents. Our binding mode analysis and stability simulations indicate their potential as selective inhibitors. The data will guide studies into their structure optimization, enhancing efficacy and drug-likeness.

Design, Synthesis, and Anti-Cancer Evaluation of Novel Water-Soluble Copper(I) Complexes Bearing Terpyridine and PTA Ligands.

This study presents a simple and energy-efficient self-assembly LAG synthetic method for novel water-soluble copper(I) complexes [Cu(terpy)(PTA)][PF6] (1) and [Cu(terpy)(PTA)2][PF6] (2). They were characterized by FT-IR, 1H, and 31P{1H} NMR spectroscopy, elemental analysis, and single-crystal/powder X-ray diffraction (for 2). The X-ray analysis of compound 2 indicates a bidentate coordination mode of terpyridine to the metal center. Variable-temperature NMR tests indicate dynamic properties for terpyridine in the case of both compounds, as well as for the PTA ligands in the case of 2. Additionally, compounds 1 and 2 exhibit interesting cytotoxic activity, which was tested on normal human dermal fibroblasts (NHDFs), human lung carcinoma (A549), human breast adenocarcinoma (MCF-7), and human cervix carcinoma (HeLa) established cell lines. In comparison to the other tested compounds, complexes 1 and 2 seem to have significantly lower IC50 values against cancer cells (A549, HeLa, MCF-7), indicating their potential as prospective anticancer agents. Moreover, both compounds show no significant toxicity towards normal skin cells (NHDFs), suggesting a certain selectivity in their action on cancer cells. Cisplatin as a reference compound also exhibited considerable cytotoxicity against cancer cells but with a low level of selectivity, which could lead to unwanted effects on normal cells. Remarkably, compounds 1 and 2 exhibit up to 30 times the cytotoxic activity of cisplatin, with a six-fold lower toxicity to normal cells. They also interact strongly with human serum albumin, suggesting potential therapeutic applications. Overall, these compounds hold significant promise as potential chemotherapeutic agents.

Synthesis, biological profile and computational insights of new derivatives of benzo [B][1,4] diazepines as prospective anticancer agents for inhibiting the CDK-2 protein

In the current work, a new series of benzo[b][1, 4] diazepines (A-1 to C-4) was synthesized and screened against three different human cancer cell lines, HepG2 (hepatocellular carcinoma), HeLa (cervical cancer) and MCF-7 (breast cancer), by employing MTT (MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. The outcomes of in vitro screening revealed that all the compounds exhibited momentous anticancer activity, most notably against the MCF-7 cell line by B1–4 compounds. Further, network pharmacology, UALCAN analysis, molecular docking, molecular dynamics (MD) simulations and density functional theory calculations were conducted to explore expression analysis, pharmacokinetics, toxicity profiles and binding interactions of the B1–4 compounds. By UALCAN, we explored the expression analysis of CDK-2 in 19 cancers. Through UALCAN, Pan-cancer analysis revealed that the expression of CDK-2 in 19 cancers was statistically significant. Among the 19 cancers, the CDK-2 expression was significantly upregulated in breast cancer (BRCA), cervical cancer (CESC) and lung carcinoma (LUSC) than normal tissues. Enzyme-docking examination revealed that B1–4 compounds exhibited significant binding affinity against the CDK-2 (PDB ID: 5IEV) drug target protein. Furthermore, MD simulations supported the docking results, which confirmed that the ligand + protein complex was in a stable conformation throughout the simulation time of 100 nanoseconds. Therefore, the present study demonstrates the potential of these benzo [b][1,4] diazepines as promising drug candidates against cancer. Communicated by Ramaswamy H. Sarma

Correction: Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent

Correction for ‘Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent’ by Matteo Fiaschi et al., Inorg. Chem. Front., 2024, 11, 2841–2862, https://doi.org/10.1039/D4QI00096J.

Synthesis and studies of aqueous-stable diruthenium aminocarbyne complexes uncovered an N-indolyl derivative as a prospective anticancer agent

Within a set of diruthenium aminocarbyne analogues, an indolyl-decorated complex, displaying optimal physicochemical properties, exhibited potent in vitro cytotoxicity against a panel of cancer cell lines, coupled with remarkable selectivity.

Cytotoxic Pt(II) complexes containing alizarin: a selective carrier for DNA metalation.

Many efforts have been made in the last few decades to selectively transport antitumor agents to their potential target sites with the aim to improve efficacy and selectivity. Indeed, this aspect could greatly improve the beneficial effects of a specific anticancer agent especially in the case of orphan tumors like the triple negative breast cancer. A possible strategy relies on utilizing a protective leaving group like alizarin as the Pt(II) ligand to reduce the deactivation processes of the pharmacophore enacted by Pt resistant cancer cells. In this study a new series of neutral mixed-ligand Pt(II) complexes bearing alizarin and a variety of diamine ligands were synthesized and spectroscopically characterized by FT-IR, NMR and UV-Vis analyses. Three Pt(II) compounds, i.e., 2b, 6b and 7b, emerging as different both in terms of structural properties and cytotoxic effects (not effective, 10.49 ± 1.21 μM and 24.5 ± 1.5 μM, respectively), were chosen for a deeper investigation of the ability of alizarin to work as a selective carrier. The study comprises the in vitro cytotoxicity evaluation against triple negative breast cancer cell lines and ESI-MS interaction studies relative to the reaction of the selected Pt(II) complexes with model proteins and DNA fragments, mimicking potential biological targets. The results allow us to suggest the use of complex 6b as a prospective anticancer agent worthy of further investigations.

In vitro evaluation of pro-apoptotic and anti-metastatic activity of Oliveria decumbens vent. extract, an endemic Persian medicinal plant, on HT-29 colorectal cancer cell line

Colorectal cancer is one of the most diagnosed and the third deadliest diseases worldwide. Despite early detection and screening have increased the survival rate, colorectal cancer still takes hundreds of thousands of lives each year globally. Near 50% of current chemotherapeutic drugs are indirect or direct descendants of compounds isolated from medicinal plants, which indicates plants are great potential sources of novel therapeutics. In this research, we studied the Oliveria decumbens Vent. which holds numerous secondary metabolites with pharmacological activities. However, no study on anticancer activity of this kind has been reported. The Oliveria decumbens Vent. is a rare, wild, and endemic Persian medicinal plant which is traditionally used in cases of gastrointestinal diseases and infections in Persian Traditional Medicine. Nevertheless, this is to be studied scientifically for the very first time. Consequently, this research is aimed to evaluate the anticancer effect of the flower Oliveria decumbens Vent. ethanolic extract against HT-29 colorectal cancer cell line using 6 techniques including cytotoxicity, cell viability by MTT assay, DPPH, gene expression assay, wound-healing assay (scratch-test) along with a DNA damage test. The ethanolic extract showed an Ic50 of 14.39 μg/ml. The results from real-time PCR demonstrated that the ethanolic extract from Oliveria decumbens effectively promoted apoptosis by increasing the expression of the pro-apoptotic gene, bax, and slightly decreasing the anti-apoptotic gene, bcl2. Additionally, the Scratch test indicated its potential in inhibiting metastasis, while DNA fragmentation confirmed its ability to induce DNA damage. Considering these findings, the Oliveria decumbens ethanolic extract holds promise as a prospective anticancer and chemotherapeutic agent, warranting further investigation in future studies.

Phytogenic One-pot Synthesis and Spectroscopic Characterization of Novel Mono Benzylated Resveratrol Hybrid Molecule Using Extracted Resveratrol from Green Grape Peels: In Silico ADMET Study and In Vitro Antitumor Activities Against Breast Cancer Cells

Background: Despite the development of numerous customized techniques for treating breast cancer, cancer patients' clinical results revealed adverse consequences in addition to chemotherapeutic drug resistance. Hence, finding therapeutic compounds with little or no side effects becomes essential in the fight against cancer. Resveratrol, a naturally occurring non-flavonoid polyphenol present in plants as a phytoalexin, is a promising therapeutic agent that has garnered the interest of several researchers due to its prodigious pharmacological and biological activities, but its unfavourable pharmacokinetic properties complicated its clinical studies. Along with several structural modifications, substitutions, etc., that have already been reported, this is the first time that a novel resveratrol analogue comprising an aromatic hetero moiety (ResD1) was synthesized using resveratrol isolated from grape (Vitis vinifera) peels as a precursor. Methods: ResD1 was synthesized by one-pot reaction using extracted and isolated resveratrol from grape peels. Structure confirmation of the isolated resveratrol and synthesized resveratrol derivative was elucidated by 1H-NMR, 13C-NMR, FTIR, and LC-MS. In silico molecular docking and ADMET study of ResD1 were carried out using AutoDock 4.2 and ADMETLab 2.0. ResD1 was evaluated for in vitro antioxidant, antimicrobial, anticancer, and CAXII gene expression as per the standard methods. Results: In silico molecular docking results revealed that ResD1 is capable of attaching to the ERα (estrogen receptor alpha) protein via hydrogen and hydrophobic bonds and has -7.12 kcal/mol as docking score. The novel derivative (IC50 = 42.8 µg/ml) exhibited better radical scavenging ability than ascorbic acid (control). The antimicrobial activities exemplify that it can induce microbial cell death for all the strains at higher concentrations. MTT assay results portrayed the potent antiproliferative activity against MCF-7 cell lines (IC50 = 155.2 µg/ml) and non-cytotoxicity for MDA-MB-231 cell lines. Moreover, the synthesized resveratrol derivative induced ROS (reactive oxygen species) levels in MCF-7 cells, indicating cytotoxicity. CAXII gene expression study showed that it downregulated the CAXII genes. Conclusion: This study serves as an example of how a newly proposed resveratrol analogue might be utilized as a viable pharmacophore for specifically targeting the ER alpha protein which will be beneficial in investigating a fresh batch of effective resveratrol mimics as prospective anticancer agents.

Automated Open-Loop in Vitro photothermal TherapyUsing Near-Infrared Emitting Graphene Quantum Dots

Graphene-based materials have been the subject of interest for photothermal therapy due to their high light to heat conversion efficiency. Graphene quantum dots (GQDs) are expected to both possess advantageous photothermal properties and facilitate visible and near-infrared (NIR) fluorescence image-tracking, while surpassing the other graphene-based materials in their biocompatibility. To test these capabilities several different GQD structures were synthesized using top-down (RGQDs from reduced graphene oxide) and bottom-up (HGQDs from molecular hyaluronic acid) approaches. RGQDs and HGQDs possess nanometer-scale sizes, are hydrophilic, and exhibit fluorescence throughout the visible and NIR. The high biocompatibility of RGQDs (1.5 mg/ml) and HGQDs (1.7 mg/ml) and substantial absorption tail in the NIR make them suitable for biological photothermal therapy applications. In aqueous suspensions of RGQDs and HGQDs, a low power (0.8 W/cm2) 808 nm NIR laser irradiation facilitates heating up to 46.0 and 47.0 °C, respectively, making them sufficient for cancer tumor ablation. In vitro photothermal studies were performed via cost-effective open-loop automated approach involving a 3D printer head controlling the laser and a thermocouple. These experiments are carried out in a 96 well plate to show that GQDs can facilitate HeLa cancer cells heating up to 54.5 and 43.5 °C from 37.0 °C, leading to the inhibition of cell viability down to 23%. GQDs’ fluorescence in the visible and NIR effectively tracks their intracellular accumulation verifying effects of photothermal treatment. The combination of therapeutic and imaging capabilities makes GQDs developed in this work highly prospective anticancer agents.

Mychonastes sp. 247 Induces Apoptosis of A549 Human Lung Cancer Cells by Promoting STRA6-Mediated Reactive Oxygen Species Production

Mychonastes sp. 247 is a newly isolated freshwater microalga. Mychonastes sp. 247 methanolic extract (ME) suppresses the growth of A549 human non-small-cell lung cancer (NSCLC) cells. However, the underlying mechanism of this anticancer effect remains unclear. The present study aimed to reveal the underlying mechanism of the anticancer effect of ME in A549 cells. The components of ME, their cytotoxicity in normal cells, and their inhibitory effect on the growth and migration of two-dimensional and three-dimensional cultured cancer cells were investigated. We also showed that ME upregulated the mRNA levels of signaling receptors and transporters of retinol (STRA6) and cytochrome P450 family 26 subfamily B member 1, and increased the protein expression of phosphorylated c-Jun N-terminal kinase, B-cell lymphoma protein 2/(Bcl-2)-associated X (Bcl-2/Bax), and cleaved caspase-3. Moreover, co-treatment with N-acetyl-L-cysteine reversed the ME-induced changes in the levels of STRA6 and reactive oxygen species (ROS), confirming their role in the ME-mediated anticancer effect. To the best of our knowledge, this is the first study elucidating the pathway by which ME induces anticancer effects in lung cancer cells. Our results reveal that ME induces NSCLC apoptosis by regulating ROS levels via the STRA6 pathway, suggesting ME as a prospective anticancer agent for lung cancer treatment.

Recent Innovations and Nano-Delivery of Actinium-225: A Narrative Review.

The actinium-225 (225Ac) radioisotope exhibits highly attractive nuclear properties for application in radionuclide therapy. However, the 225Ac radionuclide presents multiple daughter nuclides in its decay chain, which can escape the targeted site, circulate in plasma, and cause toxicity in areas such as kidneys and renal tissues. Several ameliorative strategies have been devised to circumvent this issue, including nano-delivery. Alpha-emitting radionuclides and nanotechnology applications in nuclear medicine have culminated in major advancements that offer promising therapeutic possibilities for treating several cancers. Accordingly, the importance of nanomaterials in retaining the 225Ac daughters from recoiling into unintended organs has been established. This review expounds on the advancements of targeted radionuclide therapy (TRT) as an alternative anticancer treatment. It discusses the recent developments in the preclinical and clinical investigations on 225Ac as a prospective anticancer agent. Moreover, the rationale for using nanomaterials in improving the therapeutic efficacy of α-particles in targeted alpha therapy (TAT) with an emphasis on 225Ac is discussed. Quality control measures in the preparation of 225Ac-conjugates are also highlighted.

Green synthesis of silver nanoparticles mediated Diospyros kaki L. (Persimmon): determination of chemical composition and evaluation of their antimicrobials and anticancer activities.

The eco-friendly synthesis of metallic nanoparticles (MNPs) using biological materials is an encouraging and innovativeness approach to nanotechnology. Among other synthesizing methods, biological methods are chosen because of their high efficiency and purity in many aspects. In this work, using the aqueous extract obtained from the green leaves of the D. kaki L. (DK); silver nanoparticles were synthesized in a short time and simply with an eco-friendly approach. The properties of the synthesized silver nanoparticles (AgNPs) were characterized using various techniques and measurements. In the characterization data of AgNPs, Maximum absorbance at 453.34nm wavelengths, the average size distribution of 27.12nm, the surface charge of -22.4mV, and spherical appearance were observed. LC-ESI-MS/MS analysis was used to assess the compound composition of D. kaki leaf extract. The chemical profiling of the crude extract of D. kaki leaves revealed the presence of a variety of phytochemicals, predominantly phenolics, resulting in the identification of five major high-feature compounds: two major phenolic acids (Chlorogenic acid and Cynarin), and tree flavonol glucosides (hyperoside, quercetin-3-glucoside, and quercetin-3- D-xyloside). The components with the highest concentrations were cynarin, chlorogenic acid, quercetin-3- D-xyloside, hyperoside, and quercetin-3-glucoside, respectively. Antimicrobial results were determined by a MIC assay. The biosynthesized AgNPs exhibited strong antibacterial activity against the human and food pathogen Gram (+ and -) bacteria and good antifungal activity against pathogenic yeast. It was determined that 0.03-0.050μg/mL concentrations ranges of DK-AgNPs were growth suppressive concentrations on all pathogen microorganisms. The MTT technique was used to study the cytotoxic effects of produced AgNPs on cancer cell lines (Glioblastoma (U118), Human Colorectal Adenocarcinoma (Caco-2), Human Ovarian Sarcoma (Skov-3) cancer cell lines, and Human Dermal Fibroblast (HDF) healthy cell line). It has been observed that they have a suppressive effect on the proliferation of cancerous cell lines. After 48h of treatment with Ag-NPs, the DK-AgNPs were found to be extremely cytotoxic to the CaCo-2 cell line, inhibiting cell viability by up to 59.49% at a concentration of 50gmL-1. It was found that the viability was inversely related to the DK-AgNP concentration. The biosynthesized AgNPs had dose-dependent anticancer efficacy. Because of the high concentration of bioactive chemicals in Diospyros kaki, it may be employed as a biological resource in medicinal applications. DK-AgNPs were shown to be an effective antibacterial agent as well as a prospective anticancer agent. The results provide a potential approach for the biogenic production of DK-AgNPs utilizing D. kaki aqueous leaf extract.

Biochemical Constituents and Anticancer Activities of the Essential Oils of Lannea egregia Engl. & K. Krause

Introduction: The Increase in cancer deaths has raised concerns among scientists to research on prospective anticancer agents. Lannea egregia was selected for this research because it has been identified to have ethnobotanical claims in relation to the cure of cancer in South-West Nigeria.
 Aims: To analyze the chemical constituents and determine the anticancer properties of the essential oils obtained from Lannea egregia Engl. & K. Krause Leaf, twig and stem-bark.
 Study Design: This study was designed to assay the chemical constituents of Lannea egregia and based on the ethnobotanical claims, the anticancer activities of this plant was studied.
 Place and Duration of Study: Department of Chemistry, Dipartmento di Farmacia, Via Bonanno 6, Universita di Pisa and University of Ibadan and Department of Virology, University of Ibadan, Ibadan, Nigeria. July 2018- April 2021.
 Methodology: Essential oils (EOs) from leaf, twig and stem-bark of Lannea egregia were extracted by hydro-distillation. Chemical compositions were characterized using Gas Chromatography–Mass Spectrometry (GC–MS). Cytotoxicity screenings of EOs were determined on human rhabdomyosarcoma (RD) and breast adenocarcinoma (MCF-7), using MTT [3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] cell viability assay.
 Results: Leaf, twig and stem-bark EOs gave good yields of 0.12%, 0.43% and 0.33%, respectively.
 Fifty-five, thirty-three and thirty-eight compounds were identified in leaf, twig and stem-bark EOs, accounting for 99.1%, 97.8% and 95.8% of them. Most abundant compound in leaf, stem-bark and twig EOs was β-caryophellene (28.2, 23.4 and 13.2%, respectively).
 Leaf EO displayed strong cytotoxicity against RD and MCF-7, with 50% cytotoxicity (CC50) of 1.69 and 15.81µg/ml, respectively. Twig EO exhibited good selectivity with selectivity index of 24.8 and 10.8 for RD and MCF-7, respectively.
 Conclusion: Results showed that EOs have good anticancer properties.

Ethnomedicine claim directed in-silico prediction of epidermal growth factor receptor kinase antagonist: an untapped reservoir of prospective anticancer agents

The epidermal growth factor receptor (EGFR) is a tyrosine kinase (TK) that belongs to the ErbB family and governs important cellular functions like reproduction, survival, motility, and differentiation. Overexpression, intensification, and alteration of EGFR occur in a wide range of human malignancies and are associated with tumor progression and decreased anticancer drug sensitivity. As a result, EGFR has been identified as one of the primary anticancer targets. As cancer is more likely to be poorly understood in traditional medical practices, the extrapolation of an ethnomedicine-led strategy to identifying and prioritizing anticancer medicinal plants has been questioned. Nonetheless, given the challenges of developing innovative anticancer drugs that are effective, safe, inexpensive, and widely available, ethnomedicinal studies play critical roles in identifying relevant medicinal plants that can be further investigated. This study employed pharmacophore modeling, molecular docking, and molecular dynamics simulation to develop an effective agent as an inhibitor for EGFR. The final findings revealed that the selected bioactive compound stabilized the EGFR protein. The optimum orientations of the various inhibitors was Friedelin and it was chosen and subjected, along with the FDA-approved drug, to molecular dynamics modeling to determine the molecular interaction of the medication with various mutational sites in order to deduce the suitable orientation for the inhibitors. The study also attest to the ethnomedicinal claims that ethnomedicinal plants played a huge role in anticancer drug discovery and that their exploration can change the bleak picture cancer paints in our societies today.

Seaweed-associated heterotrophic Bacillus altitudinis MTCC13046: a promising marine bacterium for use against human hepatocellular adenocarcinoma.

Since the report of the antibiotic with anticancer properties, scientists have been focusing to isolate and characterize novel anti-microbial natural products possessing anticancer activities. The current study describes the production of seaweed-associated heterotrophic Bacillus altitudinis MTCC13046 with potential anticancer properties. The bacterium was screened for its capacity to diminish the cell proliferation of the human hepatocellular adenocarcinoma (HepG2) cell line, without upsetting the normal cells. The bacterial extract showed anticancer properties in a dose-reactive form against HepG2 (IC50, half maximal inhibitory concentration ~ 29.5µg/ml) on tetrazolium bromide analysis with less significant cytotoxicity on common fibroblast (HDF) cells (IC50 ~ 77µg/ml). The potential antioxidant ability of the organic extract of B. altitudinis MTCC13046 (IC90 133µg/ml) could corroborate its capacity to attenuate the pathophysiology leading to carcinogenesis. The results of the apoptosis assay showed that the crude extracts of B. altitudinis maintained 68% viability in normal cells compared to 11% in the cancer cells (IC50 76.9µg/ml). According to the findings, B. altitudinis MTCC13046 could be used to develop prospective anticancer agents.

Design, theoretical study, druggability, pharmacokinetics and properties evolution of a new organo-bromocadmate compound as prospective anticancer agent

This study covers the synthesis and physico-chemical properties by experimental single-crystal X-ray diffraction, infrared absorption and optical absorption and comparison with theoretical calculations of a new organo-bromocadmate (II) [H3NCH2(C5H4NH)]2CdBr6·2H2O. In addition, the Quantum chemical techniques such as density functional theory (DFT) have become a powerful tool in the investigation of the molecular structure and vibrational spectrum and are finding increasing use in application related to biological systems. The optimized molecular structure and the vibrational spectra were calculated thanks to the DFT method resorting to the B3LYP function with the LanL2DZ basis set. Both the experimental and theoretical vibrational data confirms the presence of functional groups in the title compound. Subsequently, the TD-DFT approach was applied to assign the electronic transitions observed in the UV-visible spectrum measured experimentally. The obtained results have been showed that the correlation between experimental and theoretical data is in a good agreement. Besides, the thermal analysis studies were performed, but no phase transition was found in the temperature range between 25 and 600°C. Biological activity analysis suggests that the complex bound several anticancer receptors (TNF-α, COX-2, VEGF...) with high affinities, which together with molecular interactions, druggability and pharmacokinetics satisfactory explain the anticancer potential of the compound.

Design and Development of Triazole Derivatives as Prospective Anticancer Agents: A Review.

In recent years, there has been a crucial need for the design and development of novel anticancer drugs that can lessen the serious health problems and unwanted side effects associated with currently used anticancer drugs. The triazole nucleus is well-recognized to possess numerous pharmacological activities, including anticancer, as revealed by various investigations on anticancer drugs and the latest research findings. The aim of this review article is to summarise the anticancer potential of 1, 2, 3-triazole, 1, 2, 4-triazole and heterocycle-fused triazole derivatives against several human cancer cell lines, compiling research articles published between 2010 and 2021. Data were collected from PubMed, Google scholar and Research Gate using keywords "anticancer activity of 1, 2, 3-triazole derivatives", "anticancer activity of 1, 2, 4-triazole derivatives" and "anticancer activity of heterocycle- fused triazole derivatives" and reviewed comprehensively. This review examines the anticancer potential of 1,2,3-triazole coupledoleanolic acid/dithiocarbamate/ pyrido[ 2,3-d] pyrimidine derivatives, 1,2,3-triazole linked pyrimidine/1,4-naphthoquinone hybrids, and 1,2,4-triazole substituted methanone derivatives, acridine-based 1,2,4-triazole derivatives, 1,2,4-thiadiazol coupled with 1,2,4- triazole and 5-ene-thiazolo[3,2-b][1,2,4]triazole-6(5H)-one derivatives against several human cancer cell lines. This review highlights the key findings in the area of cancer therapy. Triazole derivatives possess anticancer activity against various human cancer cell lines, and hence the triazole core may act as a lead molecule for the synthesis of novel anticancer drugs.

Computational Design of Phosphatidylinositol 3-Kinase Inhibitors.

One of the most sought-after therapeutic targets for treating human cancers is the phosphoinositide 3-kinase; PI3k is an integral part of the PI3K/protein kinase B signaling arcade. This pathway is frequently activated in malignancies. Drug resistance and dose-limiting adverse effects are currently associated challenges with the existing anticancer chemotherapy. Therefore, in this research, a series of pyrimidine derivatives were designed and evaluated against human PI3K by using molecular docking analysis. The docking results were further verified by molecular dynamic simulation, which analyzed the strength of the macromolecular complex with respect to time. Compounds IV and XIV were found to be the most potent inhibitors of the human PI3K receptor with a high degree of stability within the active site of the target receptor for a timeframe of 50 ns. Thus, both of these compounds could be important drug candidates for the development of PI3K inhibitors as a prospective anticancer agent.