Effective Anticancer Drugs Research Articles

Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms.

The platinum drug, cisplatin, is considered as among the most successful medications in cancer treatment. However, due to its inherent toxicity and resistance limitations, research into other metal-based non-platinum anticancer medications with diverse mechanisms of action remains an active field. In this regard, copper complexes feature among non-platinum compounds which have shown promising potential as effective anticancer drugs. Moreover, the interesting discovery that cancer cells can alter their copper homeostatic processes to develop resistance to platinum-based treatments leads to suggestions that some copper compounds can indeed re-sensitize cancer cells to these drugs. In this work, we review copper and copper complexes bearing dithiocarbamate ligands which have shown promising results as anticancer agents. Dithiocarbamate ligands act as effective ionophores to convey the complexes of interest into cells thereby influencing the metal homeostatic balance and inducing apoptosis through various mechanisms. We focus on copper homeostasis in mammalian cells and on our current understanding of copper dysregulation in cancer and recent therapeutic breakthroughs using copper coordination complexes as anticancer drugs. We also discuss the molecular foundation of the mechanisms underlying their anticancer action. The opportunities that exist in research for these compounds and their potential as anticancer agents, especially when coupled with ligands such as dithiocarbamates, are also reviewed.

Characterization of a conjugated polysuccinimide-carboplatin compound.

Carboplatin, an advanced anticancer drug with excellent efficacy against ovarian cancer, was developed to alleviate the side effects that often occur with cisplatin and other platinum-based compounds. Our study reports the in vitro characteristics, viability, and activity of cells expressing the inducible nitric oxide synthase (iNOS) gene after carboplatin was conjugated with polysuccinimide (PSI) and administered in combination with other widely used anticancer drugs. PSI, which has promising properties as a drug delivery material, could provide a platform for prolonging carboplatin release, regulating its dosage, and improving its side effects. The iNOS gene has been shown to play an important role in both cancer cell survival and inhibition. Herein, we synthesized a PSI-carboplatin conjugate to create a modified anticancer agent and confirmed its successful conjugation. To ensure its solubility in water, we further modified the structure of the PSI-carboplatin conjugate with 2-aminoethanol groups. To validate its biological characteristics, the ovarian cancer cell line SKOV-3 and normal ovarian Chinese hamster ovary cells were treated with the PSI-carboplatin conjugate alone and in combination with paclitaxel and topotecan, both of which are used in conventional chemotherapy. Notably, PSI-carboplatin conjugation can be used to predict changes in the genes involved in cancer growth and inhibition. In conclusion, combination treatment with the newly synthesized polymer-carboplatin conjugate and paclitaxel displayed anticancer activity against ovarian cancer cells but was not toxic to normal ovarian cancer cells, resulting in the development of an effective candidate anticancer drug without severe side effects.

Targeted Therapy and Personalized Medicine.

Targeted therapy and personalized medicine are novel emerging disciplines of cancer research intended for treatment and prevention. One of the most significant advancements in modern oncology is the shift from an organ-centric strategy to a personalized strategy guided by deep molecular analysis. This shift in view, which focuses on the tumour's precise molecular changes, has paved the way for individualized treatment. Researchers and clinicians are using targeted therapies to select the best treatment available based on the molecular characterization of malignant cancer. In the treatment of a cancer, personalized medicine entails the use of genetic, immunological, and proteomic profiling to provide therapeutic alternatives as well as prognostic information about cancer. In this book, targeted therapies and personalized medicine have been covered for specific malignancies, including latest FDA-approved targeted therapies and it also sheds light on effective anti-cancer regimens and drug resistance. This will help to enhance our ability to conduct individualized health planning, make early diagnoses, and choose optimal medications for each cancer patient with predictable side effects and outcomes in a quickly evolving era. Various applications and tools' capacity have been improved for early diagnosis of cancer and the growing number of clinical trials that choose specific molecular targets reflects this predicament. Nevertheless, there are several limitations that must need to be addressed. Hence, in this chapter, we will discuss recent advancements, challenges, and opportunities in personalized medicine for various cancers, with a specific emphasis on target therapies in diagnostics and therapeutics.

An update on the recent advances and discovery of novel tubulin colchicine binding inhibitors.

Microtubules, formed by α- and β-tubulin heterodimer, are considered as a major target to prevent the proliferation of tumor cells. Microtubule-targeted agents have become increasingly effective anticancer drugs. However, due to the relatively sophisticated chemical structure of taxane and vinblastine, their application has faced numerous obstacles. Conversely, the structure of colchicine binding site inhibitors (CBSIs) is much easier to be modified. Moreover, CBSIs have strong antiproliferative effect on multidrug-resistant tumor cells and have become the mainstream research orientation of microtubule-targeted agents. This review focuses mainly on the recent advances of CBSIs during 2017-2022, attempts to depict their biological activities to analyze the structure-activity relationships and offers new perspectives for designing next generation of novel CBSIs.

Development of a novel sialic acid-conjugated camptothecin prodrug for enhanced cancer chemotherapy.

Camptothecin (CPT) is an attractive natural drug for cancer chemotherapy. However, the poor water solubility, non-targeting feature, and adverse side effects of CPT are significant obstacles to developing an effective anticancer drug. Here, for the first time, 9-thiol-sialic acid (9-SH-Sia) is coupled to CPT by forming a disulfide releasable carbonate linkage, resulting in a novel CPT prodrug (CPT-ss-Sia) that self-assembles into nanostructures in an aqueous solution. Strikingly, CPT-ss-Sia exhibited excellent in vitro properties, including enhanced water solubility, glutathione (GSH)-triggered CPT release, and increased E-lactone ring stability. Furthermore, CPT-ss-Sia had good cancer cell-killing ability comparable to CPT. Intravenous administration of CPT-ss-Sia significantly inhibited the growth of multiple types of tumors. Histological analysis showed that CPT-ss-Sia treatment significantly reduced lesions in tumor-bearing mice compared to CPT treatment. Notably, CPT-ss-Sia treatment did not adversely affect the body weight of the mice. This is the first report of the 9-SH-Sia conjugate-based prodrug. Overall, CPT-ss-Sia has broad clinical application prospects.

ВЛИЯНИЕ ЦЕЛЕНАПРАВЛЕННО СИНТЕЗИРОВАННОГО АЗОМЕТИНОВОГО ПРОИЗВОДНОГО ТЕТРАГИДРОБЕНЗТИОФЕНА-3-КАРБОКСАМИДА, НА НЕКОТОРЫЕ ПОКАЗАТЕЛИ ЛИПИДНОГО ОБМЕНА У ЗДОРОВЫХ КРЫС И В УСЛОВИЯХ ЭКСПЕРИМЕНТАЛЬНОЙ ГИПЕРЛИПИДЕМИИ

According to WHO data, cardiovascular diseases occupy a leading position in terms of the number per share of the population, both in Russia and in other countries. A prerequisite for the development of these pathologies is atherosclerosis. It is now recognized that drug therapy is leading in curbing the development of atherosclerosis and subsequent complications. In this regard, the urgency of the search for new lipid-lowering drugs aimed at the treatment of this disease is increasing. Recent studies have shown the promise of using the benzothiophene backbone for the synthesis of new effective drugs, since this core has various biological and pharmacological activities, which makes it possible to obtain effective antimicrobial, anticancer, anti-inflammatory, antioxidant, anti-tuberculosis, antidiabetic, anticonvulsant and other drugs on its basis.The purpose of this study was to study the lipid-lowering effect of the azomethine derivative 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide, a substance under the laboratory code BF-10, on some indicators of lipid metabolism in healthy rats and under pathological conditions with experimental hyperlipidemia. Atorvastatin was chosen as the reference drug. Determination of biochemical parameters of lipid metabolism in the blood serum and in the liver homogenate (the content of cholesterol, triglycerides, total lipids, LDL, VLDL and HDL) was determined by unified biochemical methods using standard Olvex Diagnosticum kits on a Dixion Torus 120 analyzer. Based on the analysis of the obtained data on the effect of the BF-10 substance on lipid metabolism, it can be concluded that they are comparable with the action of the highly effective reference drug atorvastatin, which allows us to expand information on the spectrum of biological activity of azomethine derivatives and consider the compound under the laboratory code BF-10 promising for further development.

BI-847325, a selective dual MEK and Aurora kinases inhibitor, reduces aggressive behavior of anaplastic thyroid carcinoma on an in vitro three-dimensional culture.

Anaplastic thyroid carcinoma (ATC) is the most aggressive subtype of thyroid cancer. In this study, we used a three-dimensional in vitro system to evaluate the effect of a dual MEK/Aurora kinase inhibitor, BI-847325 anticancer drug, on several cellular and molecular processes involved in cancer progression. Human ATC cell lines, C643 and SW1736, were grown in alginate hydrogel and treated with IC50 values of BI-847325. The effect of BI-847325 on inhibition of kinases function of MEK1/2 and Aurora kinase B (AURKB) was evaluated via Western blot analysis of phospho-ERK1/2 and phospho-Histone H3 levels. Sodium/iodide symporter (NIS) and thyroglobulin (Tg), as two thyroid-specific differentiation markers, were measured by qRT-PCR as well as flow cytometry and immunoradiometric assay. Apoptosis was assessed by Annexin V/PI flow cytometry and BIM, NFκB1, and NFκB2 expressions. Cell cycle distribution and proliferation were determined via P16, AURKA, and AURKB expressions as well as PI and CFSE flow cytometry assays. Multidrug resistance was evaluated by examining the expression of MDR1 and MRP1. Angiogenesis and invasion were investigated by VEGF expression and F-actin labeling with Alexa Fluor 549 Phalloidin. Western blot results showed that BI-847325 inhibits MEK1/2 and AURKB functions by decreasing phospho-ERK1/2 and phospho-Histone H3 levels. BI-847325 induced thyroid differentiation markers and apoptosis in ATC cell lines. Inversely, BI-847325 intervention decreased multidrug resistance, cell cycle progression, proliferation, angiogenesis, and invasion at the molecular and/or cellular levels. The results of the present study suggest that BI-857,325 might be an effective multi-targeted anticancer drug for ATC treatment.

Structural Determination of the Nanocomplex of Borate with Styrene-Maleic Acid Copolymer-Conjugated Glucosamine Used as a Multifunctional Anticancer Drug.

The development of effective anticancer drugs is essential for chemotherapy that specifically targets cancer tissues. We recently synthesized a multifunctional water-soluble anticancer polymer drug consisting of styrene-maleic acid copolymer (SMA) conjugated with glucosamine and boric acid (BA) (SGB complex). It demonstrated about 10 times higher tumor-selective accumulation compared with accumulation in normal tissues because of the enhanced permeability and retention effect, and it inhibited tumor growth via glycolysis inhibition, mitochondrial damage, and thermal neutron irradiation. Gaining insight into the anticancer effects of this SGB complex requires a determination of its structure. We therefore investigated the chemical structure of the SGB complex by means of nuclear magnetic resonance, infrared (IR) spectroscopy, and liquid chromatography-mass spectrometry. To establish the chemical structure of the SGB complex, we synthesized a simple model compound─maleic acid-glucosamine (MAG) conjugate─by using a maleic anhydride (MA) monomer unit instead of the SMA polymer. We obtained two MAG-BA complexes (MAGB) with molecular weights of 325 and 343 after the MAG reaction with BA. We confirmed, by using IR spectroscopy, that MAGB formed a stable complex via an amide bond between MA and glucosamine and that BA bound to glucosamine via a diol bond. As a result of this chemical design, identified via analysis of MAGB, the SGB complex can release BA and demonstrate toxicity to cancer cells through inhibition of lactate secretion in mild hypoxia that mimics the tumor microenvironment. For clinical application of the SGB complex, we confirmed that this complex is stable in the presence of serum. These findings confirm that our design of the SGB complex has various advantages in targeting solid cancers and exerting therapeutic effects when combined with neutron irradiation.

DNA damage independent inhibition of NF-kB transcription by anthracyclines.

Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning and to eviction of histones from select sites in the genome. Here we show that the extensively used anthracyclines Doxorubicin, Daunorubicin and Epirubicin decrease the transcription of nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon responsive genes in primary mouse (Mus musculus) macrophages. Using an NMR-based structural approach, we demonstrate that anthracyclines disturb the complexes formed between the NF-kB subunit RelA and its DNA binding sites. The anthracycline variants Aclarubicin, Doxorubicinone and the newly developed Dimethyl-doxorubicin, which share anticancer properties with the other anthracyclines but do not induce DNA damage, also suppressed inflammation, thus uncoupling DNA damage from the effects on inflammation. These findings have implications for anticancer therapy and for the development of novel anti-inflammatory drugs with limited side effects for life-threatening conditions such as sepsis.

FUNDC1 protects against doxorubicin-induced cardiomyocyte PANoptosis through stabilizing mtDNA via interaction with TUFM

Doxorubicin (DOX) is an effective anthracycline chemotherapeutic anticancer drug with its life-threatening cardiotoxicity severely limiting its clinical application. Mitochondrial damage-induced cardiomyocyte death is considered an essential cue for DOX cardiotoxicity. FUN14 domain containing 1 (FUNDC1) is a mitochondrial membrane protein participating in the regulation of mitochondrial integrity in multiple diseases although its role in DOX cardiomyopathy remains elusive. Here, we examined whether PANoptosis, a novel type of programmed cell death closely associated with mitochondrial damage, was involved in DOX-induced heart injury, and FUNDC1-mediated regulation of cardiomyocyte PANoptosis, if any. FUNDC1 was downregulated in heart tissues in patients with dilated cardiomyopathy (DCM) and DOX-challenged mice. FUNDC1 deficiency aggravated DOX-induced cardiac dysfunction, mitochondrial injury, and cardiomyocyte PANoptosis. Further examination revealed that FUNDC1 countered cytoplasmic release of mitochondrial DNA (mtDNA) and activation of PANoptosome through interaction with mitochondrial Tu translation elongation factor (TUFM), a key factor in the translational expression and repair of mitochondrial DNA, via its 96–133 amino acid domain. TUFM intervention reversed FUNDC1-elicited protection against DOX-induced mtDNA cytosolic release and cardiomyocyte PANoptosis. Our findings shed light toward a beneficial role of FUNDC1 in DOX cardiotoxicity and cardiomyocyte PANoptosis, thus offering therapeutic promises in DOX-induced cardiotoxicity.

Total Synthesis, Mechanism of Action, and Antitumor Efficacy of Camptothecin and Some of its Analogues.

Over the past 55 years of research, various experimental methods have been developed for the total synthesis of the anticancer camptothecin, a potent antitumor antibiotic, and its numerous active derivatives. The discoveries made in synthetic pathways of the camptothecin heterocyclic core have contributed significantly to the theory and strategy of directed organic synthesis aimed at finding effective anticancer drugs. The synthetic, medicinal chemistry of camptothecin, the development of structures of anticancer camptothecin analogues, and the mechanism of their activity in inhibiting the growth of different types of cancers, such as lung, ovarian, breast, pancreas, and stomach cancers are analyzed. Various structural modifications in the A, B, C, D, and E-rings of the camptothecin molecule have been thoroughly studied to improve bioavailability and diminish toxicity. Modern synthetic approaches to the camptothecin analogues and several semi-synthetic methods are reviewed.

Targeting tumor-intrinsic PD-L1 suppresses the progression and aggressiveness of head and neck cancer by inhibiting GSK3β-dependent Snail degradation.

PD-L1 is an immune checkpoint protein that allows cells to evade T-cell-mediated immune responses. Herein, we uncover a tumor-intrinsic mechanism of PD-L1 that is responsible for the progression and aggressiveness of HNC and reveal that the extracts of a brown alga can target the tumor-intrinsic signaling pathway of PD-L1. The biological functions of PD-L1 in the proliferation and aggressiveness of HNC cells in vitro were examined by metabolic activity, clonogenic, tumorigenicity, wound healing, migration, and invasion assays. The clinical importance of PD-L1 in the prognosis of patients with HNC was analyzed by immunohistochemistry. The relationship between PD-L1 and EMT was confirmed via western blotting, qPCR, and immunocytochemistry. Through our in silico approach, we found that PD-L1 was upregulated in HNC and was correlated with an unfavorable clinical outcome in patients with HNC. PD-L1 was crucial for promoting tumor growth, both in vitro and in vivo. High expression of PD-L1 was closely correlated with LN metastasis in OSCC. PD-L1 facilitated the cytoskeletal reorganization and aggressiveness of HNC cells. Moreover, PD-L1 enhanced the EMT of HNC cells by regulating the Snail/vimentin axis. Consistently, MEIO suppressed the PD-L1/Snail/vimentin axis, thereby inhibiting the aggressiveness of HNC cells. Inhibition of PD-L1 induced by PD-L1 silencing or MEIO treatment caused Snail degradation through a GSK3β-dependent mechanism. The tumor-intrinsic function of PD-L1 could be attributed to the regulation of the GSK3β/Snail/vimentin axis. The discovery of MEIO targeting the tumor-intrinsic function of PD-L1 may prove particularly valuable for the development of novel and effective anticancer drug candidates for HNCs overexpressing PD-L1.

Synthesis and Characterization of NUC-7738, an Aryloxy Phosphoramidate of 3'-Deoxyadenosine, as a Potential Anticancer Agent.

3'-Deoxyadenosine (3'-dA, Cordycepin, 1) is a nucleoside analogue with anticancer properties, but its clinical development has been hampered due to its deactivation by adenosine deaminase (ADA) and poor cellular uptake due to low expression of the human equilibrative transporter (hENT1). Here, we describe the synthesis and characterization of NUC-7738 (7a), a 5'-aryloxy phosphoramidate prodrug of 3'-dA. We show in vitro evidence that 7a is an effective anticancer drug in a panel of solid and hematological cancer cell lines, showing its preferential cytotoxic effects on leukemic stem cells. We found that unlike 3'-dA, the activity of 7a was independent of hENT1 and kinase activity. Furthermore, it was resistant to ADA metabolic deactivation. Consistent with these findings, 7a showed increased levels of intracellular 3'-deoxyadenosine triphosphate (3'-dATP), the active metabolite. Mechanistically, levels of intracellular 3'-dATP were strongly associated with in vitro potency. NUC-7738 is now in Phase II, dose-escalation study in patients with advanced solid tumors.

Biodegradable PEG-PCL Nanoparticles for Co-delivery of MUC1 Inhibitor and Doxorubicin for the Confinement of Triple-Negative Breast Cancer

Combating triple-negative breast cancer (TNBC) is still a problem, despite the development of numerous drug delivery approaches. Mucin1 (MUC1), a glycoprotein linked to chemo-resistance and progressive malignancy, is unregulated in TNBC. GO-201, a MUC1 peptide inhibitor that impairs MUC1 activity, promotes necrotic cell death by binding to the MUC1-C unit. The current study deals with the synthesis and development of a novel nano-formulation (DM-PEG-PCL NPs) comprising of polyethylene glycol-polycaprolactone (PEG-PCL) polymer loaded with MUC1 inhibitor and an effective anticancer drug, doxorubicin (DOX). The DOX and MUC1 loaded nanoparticles were fully characterized, and their different physicochemical properties, viz. size, shape, surface charge, entrapment efficiencies, release behavior, etc., were determined. With IC50 values of 5.8 and 2.4 nm on breast cancer cell lines, accordingly, and a combination index (CI) of < 1.0, DM-PEG-PCL NPs displayed enhanced toxicity towards breast cancer cells (MCF-7 and MDA-MB-231) than DOX-PEG-PCL and MUC1i-PEG-PCL nanoparticles. Fluorescence microscopy analysis revealed DOX localization in the nucleus and MUC1 inhibitor in the mitochondria.Further, DM-PEG-PCL NPs treated breast cancer cells showed increased mitochondrial damage with enhancement in caspase-3 expression and reduction in Bcl-2 expression.In vivo evaluation using Ehrlich Ascites Carcinoma bearing mice explicitly stated that DM-PEG-PCL NPs therapy minimized tumor growth relative to control treatment. Further, acute toxicity studies did not reveal any adverse effects on organs and their functions, as no mortalities were observed.The current research reports for the first time the synergistic approach of combination entrapment of a clinical chemotherapeutic (DOX) and an anticancer peptide (MUC1 inhibitor) encased in a diblock PEG-PCL copolymer. Incorporating both DOX and MUC1 inhibitors in PEG-PCL NPs in the designed nanoformulation has provided chances and insights for treating triple-negative breast tumors. Our controlled delivery technology is biodegradable, non-toxic, and anti-multidrug-resistant. In addition, this tailored smart nanoformulation has been particularly effective in the therapy of triple-negative breast cancer.

Transcription level differences in Taxus wallichiana var. mairei elicited by Ce3+, Ce4+ and methyl jasmonate.

Taxol is a precious and effective anticancer drug. Cerium and methyl jasmonate (MJ) have been shown to increase the yield of taxol in taxus cells. However, the mechanisms of cerium-mediated and MJ-mediated taxol biosynthesis remain unknown. RNA-Seq was applied to study the overall regulation mechanism of cerium and MJ on taxol biosynthesis and analyze the differences among T. mairei cells elicited by Ce3+, Ce4+ and MJ on transcriptional level . Using sequence homology, 179 unigenes were identified as taxol synthesis genes. Under the condition of 100 μM MJ, taxol synthesis genes were up-regulated. Notably, taxol synthesis genes were down-regulated expression at 1 mM Ce3+ and 1 mM Ce4+. Differential expression genes involved in some related functions were analyzed, such as MAPK signaling pathway and plant-pathogen interaction. Sequence alignment and phylogenetic analysis of nine differentially expressed WRKYs in our data were carried out.

Barhi date (Phoenix dactylifera) extract ameliorates hepatocellular carcinoma in male rats

Hepatocellular carcinoma (HCC) is a malignant tumor with limited treatment options. Given this fact, it may be important to develop new molecular targeted therapies from natural products, especially those which are primary sources of effective anticancer drugs with distinct mechanisms. Moreover, the complementary use of traditional herbs or fruit may increase the possibility of finding curative options for cancer. Here we explore the anticancer effects and possible molecular mechanism of Barhi date extract using an HCC rat model. Thirty two male albino rats were arbitrarily allocated into four groups: a negative control group (NCG); a positive control group (PCG), which received CCl4 (1 ml/kg b.wt./ i.p.) twice a week for three months; a Barhi date extract (400 mg/kg b.wt./day/orally) treatment group (DTG) during the third month of CCl4 administration; and a cisplatin (1.5 mg/kg b.wt./ i.p.) treatment group ( CTG) during the third month of CCl4 administration. After treatment we performed biochemical analyses of all groups to assess relative eukaryotic initiation factor 2 alpha (eIF2α), extracellular signal-regulated kinases (ERKs), protein kinase RNA-like endoplasmic reticulum kinase (PERK), poly (ADP-ribose) polymerase (PARP), and CASPASE 3 protein content, and examined expression of the genes phosphatase and tensin homolog (PTEN) and protein kinase B (AKT). We also performed an immunohistochemistry assay for alpha-fetoprotein (AFP). Our data showed higher PARP and CASPASE3 levels and liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]) in the PCG compared to the DTG and the cisplatin treatment group CTG. However, we also found a significant decrease in PTEN in the PCG relative to both the DTG and the CTG. We conclude that the anti-tumor activity of Barhi date extract may be mediated by the inhibition of cell proliferation and apoptosis via the ERK /PARP/caspase3 pathway and the AKT/ PTEN signaling pathways.

Ru(II)(ƞ6-p-cymene) Conjugates Loaded onto Graphene Oxide: An Effective pH-Responsive Anticancer Drug Delivery System.

Graphene oxide-based nanodrug delivery systems are considered one of the most promising platforms to deliver therapeutic drugs at the target site. In this study, Ru(II)(ƞ6-p-cymene) complexes containing the benzothiazole ligand were covalently anchored on graphene oxide using the ultrasonication method. The nanoconjugates GO-NCD-1 and GO-NCD-2 were characterized by FT-IR, UV-visible, 1H NMR, TGA, SEM, and TEM techniques, which confirmed the successful loading of both the complexes (NCD 1 and NCD 2) on the carrier with average particle diameter sizes of 17 ± 6.9 nm and 25 ± 6.5 nm. In vitro DNA binding studies of the nanoconjugates were carried out by employing various biophysical methods to investigate the binding interaction with the therapeutic target biomolecule and to quantify the intrinsic binding constant values useful to understand their binding affinity. Our results suggest (i) high Kb and Ksv values of the graphene-loaded conjugates (ii) effective cleavage of plasmid DNA at a lower concentration of 7.5 µM and 10 µM via an oxidative pathway, and (iii) fast release of NCD 2 at an acidic pH that could have a good impact on the controlled delivery of drug. It was found that 90% of the drug was released in an acidic pH (5.8 pH) environment in 48 h, therefore suggesting pH-responsive behavior of the drug delivery system. Molecular docking, DFT studies, and cytotoxicity activity against three cancer cell lines by SRB assay were also performed.

Recent Advances and Therapeutic Journey of Schiff Base Complexes with Selected Metals (Pt, Pd, Ag, Au) as Potent Anticancer Agents: A Review.

Schiff bases and their transition metal complexes play an important role in the field of medicine, in particular in the treatment of cancer. Since the discovery of the cisplatin anticancer activity, great efforts have focused on the rational design of metal-based anticancer drugs that can be potentially used for the treatment of cancer. However, drug resistance and significant side effects greatly limit its clinical application. This has inspired medicinal chemists to employ various strategies in the development of novel and effective anticancer drugs. Recently, a greater number of transition metal complexes have been designed and evaluated for their anticancer activities, and some of them were at different stages of clinical studies. Amongst these, platinum, palladium, gold and silver complexes have an important place within medicinal and inorganic chemistry. This review article discusses Schiff bases and their complexes with selected transition metals (Pd, Pt, Ag, Au) for anticancer activity against different cancer cell lines.

Synthesis and Anti-Cancer Applications of Benzimidazole Derivatives - Recent Studies.

Cancer is a life-threatening disease. Anti-cancer drugs are the focus of research. The heterocyclic molecules like benzimidazole occupy a central position in searching for novel and effective anti-cancer drugs. The medicinal chemists designed and synthesized several benzimidazole derivatives and conjugates to evaluate them as potential anti-cancer agents. The purpose of this compilation of literature is to cover the progress of benzimidazole-based anti-cancer agents, their synthesis, and their evaluation for cancer disease treatment. The recent literatures have been collected from various search engines and peer-reviewed journals. The compounds like benzimidazole derivatives of dehydroabietic acid, piperidyl benzimidazole carboxamide, benzimidazole-quinazolinone hybrids, benzimidazole-thiazole conjugate, and benzimidazole pendant cyanopyrimidine derivatives have been discussed in detail. This review article will help the medicinal chemists to design and synthesize benzimidazole-based molecules and evaluate them as anti-cancer agents.

Review on recent development of quinoline for anticancer activities

Quinoline is an efficient scaffold for anticancer drug development as its derivatives have shown potent results through several mechanisms like growth regulators through “apoptosis, disruption of cell migration, inhibition of angiogenesis, modulation of nuclear receptor responsiveness and cell cycle arrest, etc.,” The potential of quinoline derivatives has been proved in several cancer cell lines like breast cancer, colon cancer, lung cancer, colorectal cancer, renal cancer, etc. This review article aims to provide information about the synthesis, potential of the anticancer property, cytotoxicity, and level of clinical treatments, which could lay out the research to develop more effective quinoline-derived anticancer drugs.