Neeraj Kumar Chouhan

The clinical success of cisplatin has significantly spurred the exploration of new organometallic complexes in oncology. In this quest, repurposing of auranofin as an anticancer agent has diverted the research interest from platinum to gold complexes, as gold offers unique chemical features; among them, thioredoxin reductase (TrxR) inhibition is one of the most extensively studied anticancer pathways. In this study, we have compiled the major ligand modifications reported for gold(I) complexes and categorized them into various groups, which include sulfur-based ligands, nitrogen-containing heterocyclic ligands, carbon-derived ligands, and N-heterocyclic carbene-based ligands. Also, a few structurally distinct ligands, including propargyl-, allene-, tricarbene-, and urea-functionalized NHC frameworks, have further extended structural diversity and functional potential. The in vitro evaluation of these newly synthesized gold complexes against various cancer cell lines exhibited enhanced biological potential compared to conventional metal complexes. Comparative evaluation of the reported cytotoxicity data revealed distinct structure–activity relationships among different ligand classes, with phosphine-carbon donor and bis-NHC frameworks emerging as the most promising ligand for achieving potent anticancer activity, highlighting the critical role of ligand design in modulating anticancer activity. In addition, the use of bioactive pharmacophores derived from natural products and active pharmaceuticals has emerged as a promising design strategy for developing multitarget gold(I) complexes with enhanced therapeutic efficacy. Among the reviewed compounds, complex 68 containing a bis-NHC ligand exhibited the highest potency against HL-60 leukemia cells (GI₅₀ = 0.017 μM), while complex 49 bearing a carbon-donor ligand demonstrated remarkable activity against A549 lung cancer cells (IC₅₀ = 0.02 μM). Several other gold(I) complexes also exhibited submicromolar activity against diverse cancer cell lines, further emphasizing the importance of rational ligand engineering in enhancing anticancer efficacy. Collectively, gold(I) complexes have emerged as a promising class of anticancer agents, and the comparative evaluation presented herein provides a valuable framework for identifying potent ligand scaffolds and guiding the rational development of next-generation gold-based therapeutics. Future advances in ligand engineering may facilitate targeted drug delivery, controlled release, and multi-mechanistic therapeutic strategies to overcome toxicity and drug resistance while enhancing therapeutic efficacy.

Essential oils (EOs) extracted from spices have been integral to traditional medicine and culinary applications for millennia, known for their multifaceted pharmacological properties. This chapter delves into a comprehensive overview of the chemical composition and pharmacological evaluation of EOs derived from commonly used spices, focusing on key constituents such as terpenes, esters, phenolic, coumarins, oxides, aldehydes, and aromatic compounds. The antimicrobial, anti-inflammatory, antibiotic, antifungal, analgesic, antispasmodic, antiseptic, antiviral, aromatherapy, antioxidant, and anticancer properties of these oils are reviewed in detail, substantiated by treatment modalities and extensive in vitro and in vivo research studies. The mechanism of action, such as modulation of signalling pathways and interaction with cellular targets, along with their structure activity relationships (SARs), are discussed to elucidate how these natural compounds showcase their promising therapeutic effects. Furthermore, the chapter addresses the extraction methods, drug development processes, quality control measures, regulatory guidelines, safety considerations, challenges, and future perspectives that are essential for the development of EO-based therapeutics. By integrating traditional knowledge with modern scientific research, this chapter emphasizes the importance of essential oils from spices in pharmacology and medicinal chemistry, highlighting their key potential for developing advanced and novel therapeutic agents.

Background: Cannabidivarin, a non-psychotropic phytocannabinoid, has been identified and recognized for its antioxidant and neuroprotective properties, with potential effects on central nervous system (CNS) ailments. Objective: The purpose of the present study was to investigate the antidepressant potential of cannabidivarin in both stressed and unstressed mice via the CUMS (chronic unpredictable mild stress) model through in vivo analysis. Methods: Swiss male albino mice were exposed to the CUMS protocol daily for three consecutive weeks, resulting in depression-like behavioral symptoms. Imipramine at a dose of 15 mg/kg and cannabidivarin at doses of 50, 100, and 200 mg/kg were administered for three weeks to different groups of both stressed and unstressed mice. Results: Both imipramine (15 mg/kg) and cannabidivarin (200 mg/kg), after 21 consecutive days of administration, significantly reduced the immobility time in mice exposed to stress compared to the stressed group given saline. Neither treatment significantly affected the locomotor activity in either stressed or unstressed mice. Cannabidivarin showed antidepressant potential by reducing immobility in stressed mice, similar to imipramine, at a dose of 15 mg/kg. Additionally, both cannabidivarin (200 mg/kg) and imipramine (15 mg/kg) significantly lowered elevated plasma corticosterone, nitrite levels, and monoamine oxidase-A activity in the brains of stressed mice. Both treatments also notably reversed the chronic stress-induced decrease in catalase activity. Conclusion: In conclusion, cannabidivarin demonstrated significant antidepressant effects in mice exposed to chronic unpredictable stress using the CUMS model. These effects are likely mediated through its interaction with cannabinoid receptors, as supported by in vivo findings and the well-established role of endocannabinoid receptors in modulating responses to phytocannabinoids.

Cannabichromene, a non-psychotropic cannabinoid with antioxidant and neuroprotective properties, is hypothesized to possess antidepressant potential. This study aimed to evaluate cannabichromene’s depression-alleviating effects in mice exposed to chronic unpredictable mild stress and unstressed mice using a combination of in silico and in vivo approaches. Initially, gene targets associated with major depressive disorder were identified through GeneCards, while cannabichromene’s target genes were predicted using SwissTargetPrediction. Overlapping targets were visualized using Venny software, and protein–protein interaction networks were constructed with the STRING database. The cannabinoid receptor two genes, encoding the cannabinoid 2 receptor, emerged as a key shared target. Molecular docking studies revealed that cannabichromene exhibited a strong binding affinity to cannabinoid 2 receptors (docking score: − 9.4) compared to cannabidiol (CBD) (− 8.8) and Δ9-tetrahydrocannabinol (− 9.1). For in vivo analysis, male Swiss albino mice were subjected to chronic unpredictable mild stress for 3 weeks to induce depression-like behavior. Cannabichromene (10 and 20 mg/kg) and imipramine (15 mg/kg) were administered for 21 days. Cannabichromene at 20 mg/kg significantly reduced immobility in stressed mice, like imipramine, without affecting locomotor activity. Additionally, both cannabichromene and imipramine reduced elevated plasma nitrite and corticosterone levels and inhibited monoamine oxidase-A activity in the brain. Cannabichromene also reversed stress-induced catalase suppression. In conclusion, cannabichromene revealed a relatively substantial antidepressant character with chronic unpredictable mild stress model of depression in Swiss albino male mice, likely through interaction with cannabinoid 2 receptors encoded by the cannabinoid 2 gene, as ratified via in silico modeling and in vivo findings. This highlights cannabichromene’s potential as a novel therapeutic agent for depression after further in vitro and clinical assessments in other models. Graphical Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, deteriorating approximately 1000,000 lives. Annually rising HCC to the third most common cause of cancer mortality. Liver cancer varies geographically depending on multimodality treatments available for this heterogeneous malignancy. Conglomeration of treatments has been exercised to manage this type of cancer across distinct geographic regions. Unprecedented rise of scientific knowledge mining from the published literature is a boon to develop novel treatment modalities. We aim to focus such pharmacological aspects in HCC treatment that could effectively display the improved therapies. Extrapolating the details of liver cancer (classification, diagnosis, adequate treatments, therapeutic engineering involved in the therapy, causes, epidemiology, and survival ratio) and the result obtained through this research could be a magnificent approach in the advancement of drug delivery systems that could assist in clinical trials and further betterment of survival rate and improved therapy from this deadly cancer.

Bangham was first to develop these spherical-shaped nano-vesicles called liposomes in the early 1960s. Today, liposomes have emerged as crucial tools for bettering the delivery of drugs that majorly includes-antifungal drug, peptide hormones, enzymes, vaccines antimicrobial agents, drugs against cancer, and genetic materials. Following the different manufacturing practices and versatile properties liposomes can be categorized in various parameters of size, charge, poly-dispersity index, encapsulation efficiency, solubility properties, and lamellarity. Alteration in such parameters elevates the loading and bioavailability of a drug by giving more clear target specification, desired or controlled release. This bibliographic chapter provides a comprehensive overview of methods for the preparation of liposomes with other perspectives that majorly includes—physio-chemical characteristics, dosage regimen, advantages over other delivery systems, approved liposomal based drugs and other ongoing drugs in clinical trials. It will help researchers to breakthrough more structurally successful delivery vehicles depending upon their various physic-chemical properties.

A copper-mediated domino condensation reaction of readily accessible oxime acetates with ninhydrin is reported to afford pyrrolo[2,1-a]isoindolediones via new C–C & C–N bond formations. A wide range of oxime acetates were shown to generally participate in the reaction to produce the condensed products in excellent yields. The necessary control experiments were performed and the mechanism is proposed to involve sequentially the formation of iminium radical via Cu-mediated N–O bond cleavage of oxime acetates, addition of the radical to ninhydrin and rearrangement via ring expansion.

A mild domino rearrangement strategy for the direct access to substituted quinoline‐4‐carboxamides has been developed. This copper‐catalyzed coupling reaction of O‐acyl oximes with isatins in the presence of molecular oxygen as the sole oxidizing agent proceeds through a ring expansion of the isatins through cleavage of the two C–N bonds.