A comprehensive review on anticancer evaluation techniques.

The development of effective anticancer strategies and the improvement of our understanding of cancer need analytical tools. Utilizing a variety of analytical approaches while investigating anti-cancer medicines gives us a thorough understanding of the traits and mechanisms concerned to cancer cells, which enables us to develop potent treatments to combat them. The importance of anticancer research may be attributed to various analytical techniques that contributes to the identification of therapeutic targets and the assessment of medication efficacy, which are crucial things in expanding our understanding of cancer biology. The study looks at methods that are often used in cancer research, including cell viability assays, clonogenic assay, flow cytometry, 2D electrophoresis, microarray, immunofluorescence, western blot caspase activation assay, bioinformatics, etc. The fundamentals, applications, and how each technique analytical advances our understanding of cancer are briefly reviewed.

Discovery of highly potent PARP7 inhibitors for cancer immunotherapy.

PARP7 has been proven to play an important role in immunity. Substantial upregulation of PARP7 is observed in numerous cancerous cell types, consequently resulting in the inhibition of type Ⅰ interferon signaling pathways. Therefore, inhibiting the activity of PARP7 can enhance type Ⅰ interferon signaling to exert an anti-tumor immune response. In this study, we reported the identification of a newly found PARP7 inhibitor (XLY-1) with higher inhibitory activity (IC50 = 0.6 nM) than that of RBN-2397 (IC50 = 6.0 nM). Additionally, XYL-1 displayed weak inhibitory activity on PARP1 (IC50 > 1.0 µM). Mechanism studies showed that XYL-1 could enhance the type Ⅰ interferon signaling in vitro. Pharmacodynamic experiments showed that 50 mg/kg XYL-1 could significantly inhibit tumor growth (TGI: 76.5 %) and related experiments showed that XYL-1 could restore type Ⅰ interferon signaling and promote T cell infiltration in tumor tissues. Taken together, XYL-1 shows promise as a potential candidate for developing cancer immunotherapy agents.

Synthesis, carbonic anhydrase enzyme inhibition evaluations, and anticancer studies of sulfonamide based thiadiazole derivatives.

The sulfonamide-based thiadiazole derivatives (STDs) with different hydrophobic/hydrophilic substitutions were synthesized to investigate their potentials in carbonic anhydrase inhibition (CAI). The CAI activity of the STDs (4a-4h) and the mechanism of the inhibition kinetics were determined. STD 4f contained both methoxy and Cl groups at benzene ring in STD 4f showed the lowest IC50 value. The molecular docking study confirmed that STDs bind strongly with the active sites of the target protein PDBID 1V9E. With the help of Lineweaver-Burk plots, inhibition kinetics of PDBIR 1V9E protein with STDs were determined. Cytotoxicity was checked against human keratinocyte cell lines and the anticancer properties were determined against MCF-7 cell lines. The electrochemical method was used to investigate the binding study with DNA and CA enzymes. Anticancer studies showed that STDs have weak bonding ability to DNA and strong binding ability with CA. It is concluded that anticancer activity is through CAI rather than by DNA binding.

Synthesis of hydroxyapatite nanoparticles using Acacia falcata leaf extract and study of their anti-cancerous activity against cancerous mammalian cell lines.

This study deals with the synthesis of hydroxyapatite nanoparticles (HAPnps) mediated by Acacia falcata leaf extract. Aggregates of needle-shaped crystalline nanostructures were confirmed by FE-SEM and TEM analysis. Well-defined rings in the SAED patterns corroborated the polycrystalline nature of the HAPnps. Individual elements present in the HAPnps were attested by the specific signals for Ca, P, and O in the EDS and XPS analyses. The distinct peaks observed in the XRD spectrum matched well with the HAP hexagonal patterns with a mean crystallite size of 55.04 nm. The FTIR study unveiled the coating of the nanoparticles with the biomolecules from Acacia falcata leaves. The suspension HAPnps exhibited polydispersity (0.446) and remarkable stability (zeta potential: - 31.9 mV) as evident from DLS studies. The pore diameter was 25.7 nm as obtained from BET analysis, suggesting their mesoporous nature. The HAPnps showed the cytotoxic effect on A549 lung and MDA-MB231 breast carcinoma cell lines, with an IC50 value of 55 µg/mL. The distortion of the cell membrane and cell morphology, along with the chromatin condensation and cell necrosis on treatment with HAPnps were detected under fluorescence microscopy post acridine orange/ethidium bromide dye staining. This study reports the anti-cancerous potential of non-drug-loaded plant-mediated HAPnps. Therefore, the HAPnps obtained in this investigation could play a vital role in the biomedical field of cancer therapy.

Synthesis, Crystal Structures and Anticancer Studies of Morpholinyldithiocarbamato Cu(II) and Zn(II) Complexes.

Cu(II) and Zn(II) morpholinyldithiocarbamato complexes, formulated as [Cu(MphDTC)2] and [Zn(µ-MphDTC)2(MphDTC)2], where MphDTC is morpholinyldithiocarbamate were synthesized and characterized by elemental analysis, spectroscopic techniques and single-crystal X-ray crystallography. The molecular structure of the Cu(II) complex revealed a mononuclear compound in which the Cu(II) ion was bonded to two morpholinyl dithiocarbamate ligands to form a four-coordinate distorted square planar geometry. The molecular structure of the Zn(II) complex was revealed to be dinuclear, and each metal ion was bonded to two morpholinyl dithiocarbamate bidentate anions, one acting as chelating ligand, the other as a bridge between the two Zn(II) ions. The anticancer activity of the morpholinyldithiocarbamate ligand, Cu(II) and Zn(II) complexes were evaluated against renal (TK10), melanoma (UACC62) and breast (MCF7) cancer cells by a Sulforhodamine B (SRB) assay. Morpholinyldithiocarbamate was more active than the standard drug parthenolide against renal and breast cancer cell lines, and [Zn(µ-MphDTC)2(MphDTC)2] was the most active complex against breast cancer. The copper(II) complex had a comparable activity with the standard against renal and breast cancer cell lines but showed an enhanced potency against melanoma when compared to parthenolide.

Homo and heteromultimetallic complexes containing a group 8 transition metal and µ-diphosphine bridging ligands involved in anticancer research: A review.

Herein, we present a comprehensive review focusing on synthetic strategies, detailed structural analysis, and anticancer activity investigations of complexes following the general formula [LnM(µ-diphosphine)M'Lm] where M = group 8 metal; M' = any transition metal; µ-diphosphine = bridging ligand; Ln and Lm = ligand spheres). Both homo- and heteromultimetallic complexes will be discussed in detail. We review in vitro, in vivo and in silico anticancer activity investigations, in an attempt to draw comparisons between the various complexes and derive structure-activity relationships (SAR). This review solely focuses on complexes falling under the general formula stated above that have been studied for their anticancer activities, other complexes falling into that scheme but which have not undergone anticancer testing are not included in this review. We compare the anticancer activities of these complexes to their mononuclear counterparts, and a positive control (cisplatin) when possible and present a summary of all existing data to date and attempt to draw some conclusions on the future development of these complexes.

Modified frankincense resin stabilized gold nanoparticles for enhanced antioxidant and synergetic activity in in-vitro anticancer studies.

For the first time, Frankincense resin (FR) has been carboxymethylated to produce CMFR - AuNPs and the conjugate was utilized for the Doxorubicin drug loading. The carboxymethylation of the carboxylic, phenolic, and hydroxyl functional groups of FR has been developed into carboxymethylated Frankincense resin (CMFR). A novel CMFR-AuNPs was synthesized using the developed CMFR as a stabilizing and reducing agent. The antibacterial, antioxidant, and in-vitro anticancer activities were investigated by using CMFR-AuNPs and CMFR - AuNPs@DOX. CMFR-AuNPs demonstrated antioxidative properties by quenching DPPH radicals effectively. CMFR-AuNPs and DOX@CMFR-AuNPs demonstrated strong antibacterial activity against K. pneumoniae, S. aureus, B. subtilis, and E. coli. The cell viability was tested for CMFR -AuNPs at various concentrations of Dox-loaded CMFR -AuNPs (CMFR-AuNPs + Dox1, CMFR-AuNPs + Dox 2, & CMFR-AuNPs + Dox 3). The highest inhibition was observed on MCF-7 and HeLa cell lines using CMFR-AuNPs + Dox 3, respectively. Various techniques such as UV, FTIR, TGA, XRD, SEM, EDAX and TEM were used to characterize the designed CMFR and CMFR-AuNPs. After carboxy methylation, the amorphous nature of FR changed to crystallinity, as reflected in the XRD spectra. The XRD spectrum of the CMFR- AuNPs showed FCC structure due to the involvement of hydroxyl and carboxylic functional groups of CMFR strongly bound with the AuNPs. TGA results revealed that the CMFR is thermally more stable than FR. TEM revealed that CMFR - AuNPs were well dispersed, spherical, and hexagonal with an average diameter of 7 to 10 nm, while the size of doxorubicin loaded (DOX@CMFR-AuNPs) AuNPs was 11 to 13 nm. Green CMFR-AuNPs have the potential to enhance the drug loading and anticancer efficacy of drugs.

Green Fabrication of silver nanoparticles by leaf extract of Byttneria Herbacea Roxb and their promising therapeutic applications and its interesting insightful observations in oral cancer.

The present research was carried out to look into therapeutic insight of biosynthesized silver nanoparticles (AgNPs) by leaf extract of Byttneria herbacea Roxb (BH). The analysis of biosynthesized BH-AgNPs by UV-visible spectroscopy shows an intense surface plasmon resonance (SPR) peak at 422 nm initially and 437 nm after 30 min which certainly reveals the formation of BH-AgNPs. Fourier Infra-red Spectroscopy (FT-IR) reveals that BH-AgNPs are biosynthesized by using different bioactive compounds like O-H stretch of free hydroxyl alcohol and phenols, N-H bond of primary amines present in the leaf extract. Transmission Electron Microscope (TEM) analysis revealed that BH-AgNPs are almost spherical in nature with an average size range from of 2 nm to 12 nm. The particle size analysis by Dynamic Light Scattering (DLS) reveals that the BH-AgNPs are poly-dispersed in nature with an average size of 8 nm ± 2 nm, with a negative zeta potential value of -21 mV which reveals the biosynthesized BH-AgNPs are very stable. The BH-AgNPs (Byttneria herbacea -AgNPs) revealed excellent free radical scavenging activity and exceptional antimicrobial activity. The anti-proliferative and cytotoxic studies in KB oral cancer cells revealed biosynthesized BH-AgNPs can employ as future novel therapeutic agents in cancer treatment and other biomedical applications.

Cream production and biological in vivo/in vitro activity assessment of a novel boron-based compound derived from quercetin and phenyl boronic acid.

Boronic acids constitute an important class of synthetic intermediates due to their high chemical stability, ease of use, moderate organic Lewis acid properties, reduced reactivity profiles and numerous biological activities such as antibacterial and antioxidant. The present study documents the synthesis and characterization of a novel boronic ester compound (3,5,7-trihydroxy-2- (2-phenyl benzo [d] [1,3,2] dioxaborol-5-yl) -4H-chromen-4-a) which was derived from phenyl boronic acid and quercetin. The new boron-based compound was used in the cream formulation after evaluating its antioxidant, antibacterial, anti-enzyme, anticancer activities and electrochemical oxidation behaviour. Furthermore, the cream has been dermatologically and microbiologically tested. Also, histological evaluation of the agent was estimated on multiple rat organs by hematoxylin-eosin staining method. Antioxidant potential of the new compound was tested by ABTS cation radical (IC50: 0.11 ± 0.01 µg/mL), DPPH free radical scavenging (IC50: 0.14 ± 0.01 µg/mL), and CUPRAC (A0.5: 1.73 ± 0.16 µg/mL) methods, respectively. The compound determined to have a dominant antioxidant activity. In addition, the synthesized compound had no toxic effect on the healthy cell line (PDF), while having a very high (IC50: 18.76 ± 0.62 µg/mL) cytotoxic effect on the cancerous cell line (MCF-7). In general, the compound showed moderate acetylcholinesterase enzyme activity (IC50: 115.63 ± 1.16 µg/mL), high butyrylcholinesterase (IC50: 3.12 ± 0.04 µg/mL), antiurease (IC50: 1.10 ± 0.06 µg/mL), and antithyrosinase (IC50: 11.52 ± 0.46 µg/mL) enzyme activities. In addition, the compound was found to be effective against Escherichia coli (ATCC 25922) bacteria studied at concentrations of 6.50 mg/mL. Moreover, the test results of the boronic ester compound used in the cream formulation demonstrated that it was microbiologically and dermatologically appropriate. Histologic analysis showed that the control group and experimental group were at similar properties without significant change. The phenyl boronic acid derivative compound synthesized from quercetin may have higher biological activity potential than quercetin. Due to the high biological activity potential of the synthesized compound, it has the potential to be used in food, feed, pharmaceutical and cosmetic industries.

Isolation, identification and in vitro biological evaluation of phytochemicals from Memecylon randerianum: a medicinal plant endemic to Western Ghats of India.

The present investigation reports evaluation of phytochemical content, antimicrobial, antioxidant, antidiabetic and anticancer properties of the methanolic crude extracts prepared from Memecylon randerianum leaves. Qualitative evaluation showed the presence of carbohydrates, reducing sugars, alkaloids, phenols, flavonoids, cardiac glycosides, steroids, phytosterols, terpenoids, diterpenoids and coumarins. Quantitative estimation for phenols, flavonoids and alkaloids indicated total phenolic content 11.95 mg GAE/g, total flavonoid content 20.34 mg QE/g and total alkaloid content 316.68 mg AE/g dry weight of the crude extract respectively. The methanolic extract demonstrated effective antimicrobial activity against Escherichia coli, Staphylococcus aureus and Candida albicans. The preparation also demonstrated good antioxidant and antidiabetic activities. Anticancer activity was evaluated against breast (MCF), oral (KB) and lung (A-549) cancer cell lines and the respective IC50 values were found to be 159.81 ± 7.54 µg/mL, 240.21 ± 2.57 µg/mL and 124.17 ± 2.10 µg/mL which are comparable to IC50 values of Paclitaxel.

Synthesis of podophyllotoxin-glycosyl triazoles via click protocol mediated by silver (I)-N-heterocyclic carbenes and their anticancer evaluation as topoisomerase-II inhibitors.

Herein we report the regioselective synthesis of podophyllotoxin-Glycosyl triazole hybrids catalysed by Ag(I)-N-heterocyclic carbene (Ag(I)-NHC) in a short reaction time (∼30 min) at ambient conditions. In principle, it is the first report of Click alkyne-azide cycloaddition catalysed by Ag(I)-NHC catalyst and moreover, this new methodology yielded good results when compared with traditional CuAAC in terms of reaction time and selectivity. The synthesised compounds were further explored for in vitro anticancer activity against four human cancer cell lines Du145, HeLa, A-549, and MCF-7 and found that these synthesised compounds possess significant anticancer activity. Further, the compounds 5a and 5e were identified as promising leads due to their better activity across all cell lines than that of the standard drug etoposide. Molecular docking studies of 5a & 5e with DNA Topoisomerase-II were revealed that the free energy calculations of active compounds were in good agreement with observed IC50 values.

N-substituted hydroxynaphthalene imino-oxindole derivatives as new class of PI3-kinase inhibitor and breast cancer drug: Molecular validation and structure-activity relationship studies.

N-substituted hydroxynaphthalene imino-oxindole derivatives (5a-g) were emerged as the inhibitors of the phosphoinositide 3-kinase (PI3K), which is a crucial regulator of apoptosis or programmed cell death. Electron donor-/acceptor-substituted indole-imine (5a-g) was achieved, and the structures were elucidated by FTIR, 1H NMR, 13C NMR and HRMS. Inhibition potency of PI3Ks was assessed by competitive ELISA. Subsequently, an anticancer activity against breast cancer (MCF-7) cell lines was evaluated. In both activities, compounds 5c, 5d and 5f showed most potent activities. Percentage inhibition for anticancer activity was 78.22 ± 1.02 (5c) and 78.98 ± 1.08 (5f), and the IC50 was 2.02 ± 0.92 µm (5c) and 1.98 ± 0.18 µm (5f). Compounds 5a and 5g were found inactive for both activities, and rest all showed a moderate activity. To get more insight into the binding mode and inhibitor binding affinity, 5a-g were docked into the active site of PI3Ks p110α (PDB ID: 2ENQ). Results suggested that the hydrophobic interactions in the binding pockets of PI3Ks conquered affinity of the most favourable binding ligands (5c and 5f: inhibitory constant (ki ) = 102.4 and 128.23 nm). The SAR studies demonstrate the efficiency of 5a-g as the PI3Ks precise inhibitors with the impending to treat various cancers.

New pyrimidine based ligand capped gold and platinum nano particles: Synthesis, characterization, antimicrobial, antioxidant, DNA interaction and in vitro anticancer activities.

In this research work, we have synthesized new pyrimidine based Schiff base ligand, 2-((4,6-dimethoxypyrimidine-2-yl)methyleneenamino)-6-methoxyphenol (DPMM) capped gold (Au) and platinum (Pt) nanoparticles (NPs) by modified Brust-Schiffrin method. The characteristics of DPMM-Au NPs and DPMM-Pt NPs have been examined by UV-Visible, FTIR, SEM, TEM and powder XRD analysis. SEM analysis result shows that surface morphology of the DPMM-Au NPs and DPMM-Pt NPs are in granular and spherical shape, correspondingly. The size of the DPMM-Au NPs and DPMM-Pt NPs are approximately 38.14±4.5 and 58.64±3.0nm respectively, which confirmed by TEM analysis. The DPMM-Au NPs and DPMM-Pt NPs have potent antimicrobial against Escherichia coli, Klebsiella pneumonia, Pseudomonas fluorescens, Shigella sonnei, Staphylococcus aureus and Aspergillus niger, Candida albicans, Candida tropicalis, Mucor indicus, Rhizopus strains. The DPMM-Au NPs and DPMM-Pt NPs have good antioxidant activities than the free ligand (DPMM). The spectroscopic and viscometric measurement confirms the hydrophobic DNA binding abilities of the newly prepared DPMM capped metal NPs. Moreover, the in vitro anticancer activity of DPMM, DPMM-Au NPs and DPMM-Pt NPs against cancer (MCF-7, HeLa & HEp2) and normal (NHDF) cell lines have performed using MTT assay. These results reveals that, DPMM-Au NPs and DPMM-Pt NPs having significant cytotoxic activity against the cancer cell lines and least toxic effect on normal cell line as compared to standard drug cisplatin.

Synthesis, spectroscopic, anticancer, antibacterial and antifungal studies of Ni(II) and Cu(II) complexes with hydrazine carboxamide, 2-[3-methyl-2-thienyl methylene].

Schiff's base ligand(L) hydrazine carboxamide, 2-[3-methyl-2-thienyl methylene] and its metal complexes have been synthesized and characterized by elemental analysis, molar conductance, various spectroscopic techniques such as electronic, IR, (1)H NMR, mass, EPR. Molar conductance of complexes in DMF solution corresponds to non-electrolyte. Complexes have general composition [M(L)2X2], where M=Ni(II) and Cu(II), X=Cl(-), NO3(-), CH3COO(-) and ½SO4(2-). On the basis of above spectral studies, an octahedral geometry has been assigned for Ni(II) complexes and tetragonal geometry for Cu(II) complexes except [Cu(L)2SO4] which possesses five coordinated trigonal bipyramidal geometry. These metal complexes were also tested for their anticancer, antibacterial and antifungal activities to assess their inhibition potential. Anticancer activity of ligand and its metal complexes were evaluated using SRB fluorometric assay and Adriamycin (ADR) was applied as positive control. Schiff's base ligand and its metal complexes were screened for their antibacterial and antifungal activity against Escherichia coli, Bacillus cereus and Aspergillus niger, Aspergillus flavus, respectively. Kirby-Bauer single disk susceptibility test was used for antibacterial activity and well diffusion method for antifungal activity of the compounds on the used fungi.

Synthesis, spectroscopic, anticancer and antibacterial studies of Ni(II) and Cu(II) complexes with 2-carboxybenzaldehyde thiosemicarbazone.

Ni(II) and Cu(II) complexes of 2-carboxybenzaldehyde thiosemicarbazone (L) were synthesized and investigated by their spectral and analytical data. These newly synthesized complexes have a composition of M(L)X(H2O)2 (where M=Ni(II), Cu(II) and X=Cl(-), NO3(-), CH3COO(-)) and (L) is the tridentate Schiff base ligand. The ligand and its complexes have been characterized on the basis of analytical, molar conductivity, magnetic susceptibility measurements, FT-IR, ESR, (1)H NMR and electronic spectral analysis. All the compounds were non-electrolytic in nature. On the basis of spectral studies an octahedral geometry has been assigned for Ni(II) and a tetragonal geometry for Cu(II) complexes. The ligand and its metal complexes were screened for their anticancer studies against human breast cancer cell lines MCF-7 and calculated minimum inhibitory concentration and also for antibacterial activity using Kirby-Bauer single disk susceptibility test.

Ruthenium(III) S-methylisothiosemicarbazone Schiff base complexes bearing PPh3/AsPh3 coligand: synthesis, structure and biological investigations, including antioxidant, DNA and protein interaction, and in vitro anticancer activities.

New Ru(III) isothiosemicarbazone complexes [RuCl(EPh3)L(1-4)] (E=P or As) were obtained from the reactions between [RuCl3(EPh3)3] and bis(salicylaldehyde)-S-methylisothiosemicarbazone (H2L(1-3))/bis(2-hydroxy-naphthaldehyde)-S-methylisothiosemicarbazone (H2L(4)) ligands. The new complexes were characterized by using elemental analyses and various spectral (UV-Vis, IR, (1)H NMR, FAB-Mass and EPR) methods. The redox properties of the complexes were studied by using cyclic voltammetric method. The new complexes were subjected to various biological investigations such as antioxidant assays involving DPPH radical, hydroxyl radical, nitric oxide radical and hydrogen peroxide, DNA/protein interaction studies and in vitro cytotoxic studies against human breast cancer cell line (MCF-7). New complexes showed excellent free radicals scavenging ability and could bind with DNA via intercalation. Protein binding studies using fluorescence spectroscopy showed that the new complexes could bind strongly with bovine serum albumin (BSA). Photo cleavage experiments using DNA of E-coli bacterium exhibited the DNA cleavage ability of the complexes. Further, the in vitro anticancer activity studies on the new complexes against MCF-7 cell line exhibited the ability of Ru(III) isothiosemicarbazone complexes to suppress the development of malignant neoplastic disease cells.