Anticancer Chemotherapeutics Research Articles

Novel platinum therapeutics induce rapid cancer cell death through triggering intracellular ROS storm

Induction of reactive oxygen species (ROS) production in cancer cells plays a critical role for cancer treatment. However, therapeutic efficiency remains challenging due to insufficient ROS production of current ROS inducers. We designed a novel platinum (Pt)-based drug named “carrier-platin” that integrates ultrasmall Pt-based nanoparticles uniformly confined within a poly(amino acids) carrier. Carrier-platin dramatically triggered a burst of ROS in cancer cells, leading to cancer cell death as quick as 30 min. Unlike traditional Pt-based drugs which induce cell apoptosis through DNA intercalation, carrier-platin with superior ROS catalytic activities induces a unique pattern of cancer cell death that is neither apoptosis nor ferroptosis and operates independently of DNA damage. Importantly, carrier-platin demonstrates superior anti-tumor efficacy against a broad spectrum of cancers, particularly those with multidrug resistance, while maintaining minimal systemic toxicity. Our findings reveal a distinct mechanism of action of Pt in cancer cell eradication, positioning carrier-platin as a novel category of anti-cancer chemotherapeutics.

Current scenario of fused pyrimidines with in vivo anticancer therapeutic potential.

Cancer, characterized by uncontrolled cell growth and metastasis, is responsible for nearly one in six deaths and represents a severe threat to public health worldwide. Chemotherapy can substantially improve the quality of life and survival of patients with cancer, but anticancer chemotherapeutics are associated with a range of adverse effects. Moreover, almost all currently available anticancer chemotherapeutics could develop drug resistance over a period of time of application in cancer patients and ultimately lead to cancer relapse and death in 90% of patients, creating an urgent need to develop new anticancer agents. Fused pyrimidines trait the inextricable part of DNA and RNA and are vital in numerous biological processes. Fused pyrimidines can act on various biological cancer targets and have the potential to address drug resistance. In addition, more than 20 fused pyrimidines have already been approved for clinical treatment of different cancers and occupy a prominent place in the current therapeutic arsenal, revealing that fused pyrimidines are privileged scaffolds for the development of novel anticancer chemotherapeutics. The purpose of this review is to summarize the current scenario of fused pyrimidines with in vivo anticancer therapeutic potential along with their acute toxicity, metabolic profiles as well as pharmacokinetic properties, toxicity and mechanisms of action developed from 2020 to the present to facilitate further rational exploitation of more effective candidates.

In vitro and in vivo activities of a trithiolato-diRuthenium complex conjugated with sulfadoxine against the apicomplexan parasite Toxoplasma gondii

Organometallic compounds, including Ruthenium complexes, have been widely developed as anti-cancer chemotherapeutics, but have also attracted much interest as potential anti-parasitic drugs. Recently hybrid drugs composed of organometallic Ruthenium moieties that were complexed to different antimicrobial agents were synthesized. One of these compounds, a trithiolato-diRuthenium complex (RU) conjugated to sulfadoxine (SDX), inhibited proliferation of Toxoplasma gondii tachyzoites grown in human foreskin fibroblast (HFF) monolayers with an IC50 < 150 nM, while SDX and the non-modified RU complex applied either individually or as an equimolar mixture were much less potent. In addition, conjugation of SDX to RU lead to decreased HFF cytotoxicity. RU-SDX did not impair the in vitro proliferation of murine splenocytes at concentrations ranging from 0.1 to 0.5 μM but had an impact at 2 μM, and induced zebrafish embryotoxicity at 20 μM, but not at 2 or 0.2 μM. RU-SDX acted parasitostatic but not parasiticidal, and induced transient ultrastructural changes in the mitochondrial matrix of tachyzoites early during treatment. While other compounds that target the mitochondrion such as the uncouplers FCCP and CCCP and another trithiolato-Ruthenium complex conjugated to adenine affected the mitochondrial membrane potential, no such effect was detected for RU-SDX. Evaluation of the in vivo efficacy of RU-SDX in a murine T. gondii oocyst infection model comprised of non-pregnant outbred CD1 mice showed no effects on the cerebral parasite burden, but reduced parasite load in the eyes and in heart tissue.

Targeting Telomere Dynamics as an Effective Approach for the Development of Cancer Therapeutics.

Telomere is a protective structure located at the end of chromosomes of eukaryotes, involved in maintaining the integrity and stability of the genome. Telomeres play an essential role in cancer progression; accordingly, targeting telomere dynamics emerges as an effective approach for the development of cancer therapeutics. Targeting telomere dynamics may work through multifaceted molecular mechanisms; those include the activation of anti-telomerase immune responses, shortening of telomere lengths, induction of telomere dysfunction and constitution of telomerase-responsive drug release systems. In this review, we summarize a wide variety of telomere dynamics-targeted agents in preclinical studies and clinical trials, and reveal their promising therapeutic potential in cancer therapy. As shown, telomere dynamics-active agents are effective as anti-cancer chemotherapeutics and immunotherapeutics. Notably, these agents may display efficacy against cancer stem cells, reducing cancer stem levels. Furthermore, these agents can be integrated with the capability of tumor-specific drug delivery by the constitution of related nanoparticles, antibody drug conjugates and HSA-based drugs.

Arterial Stiffness Changes in Adult Cancer Patients Receiving Anticancer Chemotherapy: A Real-World Bicentric Experience.

Background Chemotherapy correlates to acute and long-term cardiotoxicity, is reflected clinically by myocardial and vascular endothelial dysfunction, and can cause cardiovascular complications. Thus, early diagnosis of cardiovascular disease in cancer patients undergoing anti-cancer treatment is necessary to enhance long-term survival. Our principal objective in this study was to discern the impact of specific anti-cancer chemotherapeutics and biologics on arterial stiffness alterations before and after the administration. Methods Conducted at Mustafa Bacha University Hospital, Algeria, the study focused on arterial stiffness in anti-cancer chemotherapy patients. Assessments included blood pressure, diabetes, and dyslipidemia, with precise measurements using validated systems, particularly pulse wave velocity (PWV). Various chemotherapy protocols were applied, and statistical analysis with R software (R Foundation for Statistical Computing, Vienna, Austria) maintained a significance level of p=0.05. Key outcomes centered on carotid-femoral PWV and secondary endpoints such as central and peripheral pressures and pulse pressure (PP). Univariate and bivariate analyses were conducted using appropriate statistical tests. Results A comparative prospective observational study was completed on 58 patients (34 women and 24 men; mean age: 52.64 +/- 12.12 years) treated with anti-cancer chemotherapy agents. Our evaluation included a complete clinical exam, electrocardiogram, Doppler echocardiography, and applanation tonometry with arterial stiffness measurement using PWV. Patients presented significantly higher levels of carotid-femoral PWV, regardless of the chosen chemotherapy protocol, with no return to the initial level after one year of stopping treatment (p-value < 0.01). Moreover, this increase was more significant in patients with diabetes and hypertension and patients treated with monoclonal antibodies or intercalants. Conclusion This prospective study shows that chemotherapy patients have elevated arterial stiffness, emphasizing the need to assess PWV and monitor cardiovascular risk factors. PP measurement with PWV could improve risk management.

Recent Advances in Structural Optimization of Quinazoline-Based Protein Kinase Inhibitors for Cancer Therapy (2021-Present).

Cancer is a complicated, multifaceted disease that can impact any organ in the body. Various chemotherapeutic agents have a low selectivity and are very toxic when used alone or in combination with others. Resistance is one of the most important hurdles that develop due to the use of many anticancer therapeutics. As a result, treating cancer requires a target-specific palliative care strategy. Remarkable scientific discoveries have shed light on several of the molecular mechanisms underlying cancer, resulting in the development of various targeted anticancer agents. One of the most important heterocyclic motifs is quinazoline, which has a wide range of biological uses and chemical reactivities. Newer, more sophisticated medications with quinazoline structures have been found in the last few years, and great strides have been made in creating effective protocols for building these pharmacologically active scaffolds. A new class of chemotherapeutic agents known as quinazoline-based derivatives possessing anticancer properties consists of several well-known compounds that block different protein kinases and other molecular targets. This review highlights recent updates (2021-2024) on various quinazoline-based derivatives acting against different protein kinases as anticancer chemotherapeutics. It also provides guidance for the design and synthesis of novel quinazoline analogues that could serve as lead compounds.

High-nuclearity Luminescent Lanthanide Nanocages for Tumor Drug Delivery.

There is an unmet need for easy-to-visualize drug carriers that can deliver therapeutic cargoes deep into solid tumors. Herein, we report the preparation of ultrasmall luminescent imine-based lanthanide nanocages, Eu60 and Tb60 (collectively Ln60 ), designed to encapsulate anticancer chemotherapeutics for tumor therapy. The as-prepared nanocages possess large cavities suitable for the encapsulation of doxorubicin (DOX), yielding DOX@Ln60 nanocages with diameters around 5 nm. DOX@Ln60 are efficiently internalized by breast cancer cells, allowing the cells to be visualized via the intrinsic luminescent property of Ln(III). Once internalized, the acidic intracellular microenvironment promotes imine bond cleavage and the release of the loaded DOX. DOX@Ln60 inhibits DNA replication and triggers tumor cell apoptosis. In a murine triple negative breast cancer (TNBC) model, DOX@Ln60 was found to inhibit tumor growth with negligible side effects on normal tissues. It proved more effective than various controls, including DOX and Ln60 . The present nanocages thus point the way to the development of precise nanomedicines for tumor imaging and therapy.

Three Rounds of Stability-Guided Optimization and Systematical Evaluation of Oncolytic Peptide LTX-315.

Oncolytic peptides represent promising novel candidates for anticancer treatments. In our efforts to develop oncolytic peptides possessing both high protease stability and durable anticancer efficiency, three rounds of optimization were conducted on the first-in-class oncolytic peptide LTX-315. The robust synthetic method, in vitro and in vivo anticancer activity, and anticancer mechanism were investigated. The D-type peptides represented by FXY-12 possessed significantly improved proteolytic stability and sustained anticancer efficiency. Strikingly, the novel hybrid peptide FXY-30, containing one FXY-12 and two camptothecin moieties, exhibited the most potent in vitro and in vivo anticancer activities. The mechanism explorations indicated that FXY-30 exhibited rapid membranolytic effects and induced severe DNA double-strand breaks to trigger cell apoptosis. Collectively, this study not only established robust strategies to improve the stability and anticancer potential of oncolytic peptides but also provided valuable references for the future development of D-type peptides-based hybrid anticancer chemotherapeutics.

A Critical Appraisal of the Protective Activity of Polyphenolic Antioxidants against Iatrogenic Effects of Anticancer Chemotherapeutics.

Polyphenolic compounds, encompassing flavonoids (e.g., quercetin, rutin, and cyanidin) and non-flavonoids (e.g., gallic acid, resveratrol, and curcumin), show several health-related beneficial effects, which include antioxidant, anti-inflammatory, hepatoprotective, antiviral, and anticarcinogenic properties, as well as the prevention of coronary heart diseases. Polyphenols have also been investigated for their counteraction against the adverse effects of common anticancer chemotherapeutics. This review evaluates the outcomes of clinical studies (and related preclinical data) over the last ten years, with a focus on the use of polyphenols in chemotherapy as auxiliary agents acting against oxidative stress toxicity induced by antitumor drugs. While further clinical studies are needed to establish adequate doses and optimal delivery systems, the improvement in polyphenols' metabolic stability and bioavailability, through the implementation of nanotechnologies that are currently being investigated, could improve therapeutic applications of their pharmaceutical or nutraceutical preparations in tumor chemotherapy.

Anticancer effect of organotin complexes derived from 2,6-naphthalenedicarboxylic acid by enhancing the ROS generation

Enhancing ROS generation is crucial for anti-metastasis and anti-proliferation effects in anticancer chemotherapeutics. Herein, five organotin complexes [(Ph3Sn)2L] (1) [(R3Sn)2L]n (R = Et 2, R = n-Bu 3), [(n-Bu3Sn)2L(4,4′-bpe)]n (4), [(n-Bu3Sn)2L(4,4′-bipy)]n (5) were synthesized based on appropriate organotin precursors, 2,6-naphthalenedicarboxylic acid (H2L) and auxiliary ligand (4,4′-bipy = 4,4′-bipyridine, 4,4′-bpe = 1,2-di(4-pyridyl)ethylene). It was found that complex 1 exhibits a tetra-coordinated monomeric structure, complexes 2 and 3 show the 2D coordination polymer, and complexes 4 and 5 display the 1D chain with the central tin atoms as all penta-coordinated. These complexes showed high anti-tumor activity in vitro against four cancer cells (A549, HCT116, HepG-2 and HeLa), with IC50 values changed from 0.34±0.01 μM to 25.54 ± 1.55 μM. Additionally, complex 1 could be effective in inhibiting HepG-2 cell migration. Simultaneously, anticancer mechanism studies show that complex 1 induces excessive ROS production in HepG-2 cells, which in turn leads to the occurrence of ROS-induced downstream events, followed by the disintegration of the redox balance, depolarization of mitochondrial membrane potential, nucleus damage and ultimately apoptosis. This work suggests that enhancing the ability of organotin complexes to generate reactive oxygen species and disrupt intracellular redox balance may be a promising anticancer strategy.

Current development of pyrazole-azole hybrids with anticancer potential.

Chemotherapy is a critical treatment modality for cancer patients, but multidrug resistance remains one of the major challenges in cancer therapy, creating an urgent need for the development of novel potent chemical entities. Azoles, particularly pyrazole, could interact with different biological targets and exhibit diverse biological properties including anticancer activity. Many clinically used anticancer agents own an azole moiety, demonstrating that azoles are privileged and pivotal templates in the discovery of novel anticancer chemotherapeutics. The present article is an attempt to highlight the recent advances in pyrazole-azole hybrids with anticancer potential and discuss the structure-activity relationships, covering articles published from 2018 to present, to facilitate the rational design of more effective anticancer candidates.

Refinement of safety and efficacy of anti-cancer chemotherapeutics by tailoring their site-specific intracellular bioavailability through transporter modulation.

Low intracellular bioavailability, off-site toxicities, and multi drug resistance (MDR) are the major constraints involved in cancer chemotherapy. Many anticancer molecules fail to become a good lead in drug discovery because of their poor site-specific bioavailability. Concentration of a molecule at target sites is largely varied because of the wavering expression of transporters. Recent anticancer drug discovery strategies are paying high attention to enhance target site bioavailability by modulating drug transporters. The level of genetic expression of transporters is an important determinant to understand their ability to facilitate drug transport across the cellular membrane. Solid carrier (SLC) transporters are the major influx transporters involved in the transportation of most anti-cancer drugs. In contrast, ATP-binding cassette (ABC) superfamily is the most studied class of efflux transporters concerning cancer and is significantly involved in efflux of chemotherapeutics resulting in MDR. Balancing SLC and ABC transporters is essential to avoid therapeutic failure and minimize MDR in chemotherapy. Unfortunately, comprehensive literature on the possible approaches of tailoring site-specific bioavailability of anticancer drugs through transporter modulation is not available till date. This review critically discussed the role of different specific transporter proteins in deciding the intracellular bioavailability of anticancer molecules. Different strategies for reversal of MDR in chemotherapy by incorporation of chemosensitizers have been proposed in this review. Targeted strategies for administration of the chemotherapeutics to the intracellular site of action through clinically relevant transporters employing newer nanotechnology-based formulation platforms have been explained. The discussion embedded in this review is timely considering the current need of addressing the ambiguity observed in pharmacokinetic and clinical outcomes of the chemotherapeutics in anti-cancer treatment regimens.

Repurposing anti-parasite benzimidazole drugs as selective anti-cancer chemotherapeutics

Cancer chemotherapy is generally associated with many severe adverse effects. Many cancer studies are currently focused on repurposing conventional non-toxic anti-parasite drugs for cancer treatment. Since cancer cells and parasites have many features in common, some anti-parasite drugs such as benzimidazoles have been recently found to possess the anti-cancer activity. Benzimidazoles act against cancer by inhibiting tubulin polymerization, inducing cancer cell apoptosis, arresting cell cycle and over-generating reactive oxygen specimen. In this review, we summarize the anticancer features of these drugs in recent investigations, lead to reconsideration of benzimidazoles as a family of anti-cancer chemotherapeutics with non-toxicity or low toxicity to the normal cells and tissues. We particularly highlight the recent progresses using nanoformulations for enhanced cancer therapy and provide our prospects in the future research.

Alkaloids as Natural NRF2 Inhibitors: Chemoprevention and Cytotoxic Action in Cancer.

Being a controller of cytoprotective actions, inflammation, and mitochondrial function through participating in the regulation of multiple genes in response to stress-inducing endogenous or exogenous stressors, the transcription factor Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) is considered the main cellular defense mechanism to maintain redox balance at cellular and tissue level. While a transient activation of NRF2 protects normal cells under oxidative stress, the hyperactivation of NRF2 in cancer cells may help them to survive and to adapt under oxidative stress. This can be detrimental and related to cancer progression and chemotherapy resistance. Therefore, inhibition of NRF2 activity may be an effective approach for sensitizing cancer cells to anticancer therapy. In this review, we examine alkaloids as NRF2 inhibitors from natural origin, their effects on cancer therapy, and/or as sensitizers of cancer cells to anticancer chemotherapeutics, and their potential clinical applications. Alkaloids, as inhibitor of the NRF2/KEAP1 signaling pathway, can have direct (berberine, evodiamine, and diterpenic aconitine types of alkaloids) or indirect (trigonelline) therapeutic/preventive effects. The network linking alkaloid action with oxidative stress and NRF2 modulation may result in an increased NRF2 synthesis, nuclear translocation, as well in a downstream impact on the synthesis of endogenous antioxidants, effects strongly presumed to be the mechanism of action of alkaloids in inducing cancer cell death or promoting sensitivity of cancer cells to chemotherapeutic agents. In this regard, the identification of additional alkaloids targeting the NRF2 pathway is desirable and the information arising from clinical trials will reveal the potential of these compounds as a promising target for anticancer therapy.

The current scenario of furoxan hybrids with anticancer potential

AbstractCancer is one of the most common and deadliest diseases affecting millions of human beings globally. Treatment of cancer has achieved great advancements, and chemotherapy remains one of the most important means. However, the chemotherapy suffers from apparent limitations including drug resistance, systemic toxicity, adverse effects, and tumor recurrence, creating an urgent demand to develop novel anticancer chemotherapeutics. Furoxan derivatives could exert anticancer activity via releasing high concentrations of nitric oxide (NO), which could induce cellular apoptosis, arrest cell cycle, inhibit the migration and invasion of cells, and suppress angiogenesis. Hence, furoxan derivatives demonstrated potent in vitro and in vivo anticancer efficiency. In particular, furoxan hybrids, combination of other anticancer pharmacophores with furoxan moiety, demonstrated significant therapeutic effects on various cancers including drug‐resistant forms since these derivatives could act on multiple targets in cancer cells simultaneously. Accordingly, furoxan hybrids constitute an important source in the development of novel chemotherapeutic agents with anticancer activity. This review is to highlight the current scenario of furoxan hybrids with anticancer potential, covering articles published from 2012 to present. The structure–activity relationships and mechanisms of action are discussed to continuously open up a map for the remarkable exploration of more effective candidates.

Composite Hydrogels with Included Solid-State Nanoparticles Bearing Anticancer Chemotherapeutics.

Hydrogels have many useful physicochemical properties which, in combination with their biocompatibility, suggest their application as a drug delivery system for the local and prorogated release of drugs. However, their drug-absorption capacity is limited because of the gel net's poor adsorption of hydrophilic molecules and in particular, hydrophobic molecules. The absorption capacity of hydrogels can be increased with the incorporation of nanoparticles due to their huge surface area. In this review, composite hydrogels (physical, covalent and injectable) with included hydrophobic and hydrophilic nanoparticles are considered as suitable for use as carriers of anticancer chemotherapeutics. The main focus is given to the surface properties of the nanoparticles (hydrophilicity/hydrophobicity and surface electric charge) formed from metal and dielectric substances: metals (gold, silver), metal-oxides (iron, aluminum, titanium, zirconium), silicates (quartz) and carbon (graphene). The physicochemical properties of the nanoparticles are emphasized in order to assist researchers in choosing appropriate nanoparticles for the adsorption of drugs with hydrophilic and hydrophobic organic molecules.

Discovery of New Quinoline-Based Diarylamides as Potent B-RAFV600E/C-RAF Kinase Inhibitors Endowed with Promising In Vitro Anticancer Activity

The emergence of cancer resistance to targeted therapy represents a significant challenge in cancer treatment. Therefore, identifying new anticancer candidates, particularly those addressing oncogenic mutants, is an urgent medical demand. A campaign of structural modifications has been conducted to further optimize our previously reported 2-anilinoquinoline-diarylamides conjugate VII as a B-RAFV600E/C-RAF inhibitor. Considering the incorporation of a methylene bridge between the terminal phenyl and cyclic diamine, focused quinoline-based arylamides have been tailored, synthesized, and biologically evaluated. Among them, the 5/6-hydroxyquinolines 17b and 18a stood out as the most potent members, with IC50 values of 0.128 µM, 0.114 µM against B-RAFV600E, and 0.0653 µM, 0.0676 µM against C-RAF. Most importantly, 17b elicited remarkable inhibitory potency against the clinically resistant B-RAFV600K mutant with an IC50 value of 0.0616 µM. The putative binding mode of 17b and 18a were studied by molecular docking and molecular dynamics (MD). Moreover, the antiproliferative activity of all target compounds has been examined over a panel of NCI-60 human cancer cell lines. In agreement with cell-free assays, the designed compounds exerted superior anticancer impact over the lead quinoline VII against all cell lines at a 10 µM dose. Notably, both 17b and 18b showed highly potent antiproliferative activity against melanoma cell lines with growth percent under -90% (SK-MEL-29, SK-MEL-5, and UACC-62) at a single dose, while 17b maintained potency with GI50 values of 1.60-1.89 µM against melanoma cell lines. Taken together, 17b, a promising B-RAFV600E/V600K and C-RAF kinase inhibitor, may serve as a valuable candidate in the arsenal of anticancer chemotherapeutics.

Drug-Drug Interactions of Cannabidiol with Standard-of-Care Chemotherapeutics.

Cannabidiol (CBD) is an easily accessible and affordable Marijuana (Cannabis sativa L.) plant derivative with an extensive history of medical use spanning thousands of years. Interest in the therapeutic potential of CBD has increased in recent years, including its anti-tumour properties in various cancer models. In addition to the direct anticancer effects of CBD, preclinical research on numerous cannabinoids, including CBD, has highlighted their potential use in: (i) attenuating chemotherapy-induced adverse effects and (ii) enhancing the efficacy of some anticancer drugs. Therefore, CBD is gaining popularity as a supportive therapy during cancer treatment, often in combination with standard-of-care cancer chemotherapeutics. However, CBD is a biologically active substance that modulates various cellular targets, thereby possibly resulting in unpredictable outcomes, especially in combinations with other medications and therapeutic modalities. In this review, we summarize the current knowledge of CBD interactions with selected anticancer chemotherapeutics, discuss the emerging mechanistic basis for the observed biological effects, and highlight both the potential benefits and risks of such combined treatments. Apart from the experimental and preclinical results, we also indicate the planned or ongoing clinical trials aiming to evaluate the impact of CBD combinations in oncology. The results of these and future trials are essential to provide better guidance for oncologists to judge the benefit-versus-risk ratio of these exciting treatment strategies. We hope that our present overview of this rapidly advancing field of biomedicine will inspire more preclinical and clinical studies to further our understanding of the underlying biology and optimize the benefits for cancer patients.

Multistate Redox-Switchable Ion Transport Using Chalcogen-Bonding Anionophores.

Synthetic supramolecular transmembrane anionophores have emerged as promising anticancer chemotherapeutics. However, key to their targeted application is achieving spatiotemporally controlled activity. Herein, we report a series of chalcogen-bonding diaryl tellurium-based transporters in which their anion binding potency and anionophoric activity are controlled through reversible redox cycling between Te oxidation states. This unprecedented in situ reversible multistate switching allows for switching between ON and OFF anion transport and is crucially achieved with biomimetic chemical redox couples.

Different routes for the construction of biologically active diversely functionalized bicyclo[3.3.1]nonanes: an exploration of new perspectives for anticancer chemotherapeutics.

Cancer is the second most high-morbidity disease throughout the world. From ancient days, natural products have been known to possess several biological activities, and research on natural products is one of the most enticing areas where scientists are engrossed in the extraction of valuable compounds from various plants to isolate many life-saving medicines, along with their other applications. It has been noticed that the bicyclo[3.3.1]nonane moiety is predominant in most biologically active natural products owing to its exceptional characteristics compared to others. Many derivatives of bicyclo[3.3.1]nonane are attractive to researchers for use in asymmetric catalysis or as potent anticancer entities along with their successful applications as ion receptors, metallocycles, and molecular tweezers. Therefore, this review article discusses several miscellaneous synthetic routes for the construction of bicyclo[3.3.1]nonanes and their heteroanalogues in association with the delineation of their anticancer activities with few selective compounds.