Anticancer potential and structure activity studies of purine and pyrimidine derivatives: an updated review.

Cancer is the world's leading cause of death impacting millions of lives globally. The increasing research over the past several decades has focused on the development of new anticancer drugs, but still cancer continues to be a global health challenge. Thus, several new alternative therapeutic strategies have been tried for the drug design and discovery. Purine and pyrimidine heterocyclic compounds have received attention recently due to their potential in targeting various cancers. It is evident from the recently published data over the last decade that incorporation of the purine and pyrimidine rings in the synthesized derivatives resulted in the development of potent anticancer molecules. This review presents synthetic strategies encompassing several examples of recently developed purine and pyrimidine-containing compounds as anticancer agents. In addition, their structure-activity relationships are represented in the schemes indicating the fragment or groups that are essential for the enhanced anticancer activities. Purine and pyrimidines combined with other heterocyclic compounds have resulted in many novel anticancer molecules that address the challenges of drug resistance. The purine and pyrimidine derivatives showed significantly enhanced anticancer activities against targeted receptor proteins with numerous compounds with an IC50 value in the nanomolar range. The review will support medicinal chemists and contribute in progression and development of synthesis of more potent chemotherapeutic drug candidates to mitigate the burden of this dreadful disease.

Anticancer Potential of the S-Heterocyclic Ring Containing Drugs and its Bioactivation to Reactive Metabolites.

Sulfur-containing heterocyclic derivatives have been disclosed for binding with a wide range of cancer-specific protein targets. Various interesting derivatives of sulfur-containing heterocyclics such as benzothiazole, thiazole, thiophene, thiazolidinedione, benzothiophene, and phenothiazine, etc have been shown to inhibit diverse signaling pathways implicated in cancer. Significant progress has also been made in molecular targeted therapy against specific enzymes such as kinase receptors due to potential binding interactions inside the ATP pocket. Sulfur-containing heterocyclic ring metal complexes i. e., benzothiazole, thiazole, thiophene, benzothiophene and phenothiazines are among the most promising active anticancer compounds. However, sulfur heteroaromatic rings, particularly thiophene, are of high structural alert due to their metabolism to reactive metabolites. The mere presence of a structural alert itself does not determine compound toxicity therefore, this review focuses on some specific findings that shed light on factors influencing the toxicity. In the current review, synthetic strategies of introducing the sulfur core ring in the synthesized derivatives are discussed with their structure-activity relationships to enhance our understanding of toxicity mechanisms and develop safer therapeutic options. The sulfur-containing marketed anticancer drugs included in this review direct the synthesis of novel compounds and will help in the development of potent, safer sulfur-based anticancer drugs in near future.

Molecular Docking and Cognitive Impairment Attenuating Effect of Phenolic Compound Rich Fraction of Trianthema portulacastrum in Scopolamine Induced Alzheimer's Disease Like Condition.

Dementia is considered as the frequent cause of neurodegenerative mental disorder such as Alzheimer's disease (AD) amongst elderly people. Free radicals as well as cholinergic deficit neurons within nucleus basalis magnocellularis demonstrated to attribute with aggregation of ß amyloid which further acts as an essential hallmark in AD. Various phenolic phytoconstituents exists in Trianthema portulastrum (TP) leaves have been reported as active against various neurological disorders. The current investigation was undertaken to evaluate the antiamnesic potential of butanol fraction of TP hydroethanolic extract (BFTP) by utilizing rodent models of elevated plus maze (EPM) and Hebbs William Maze (HWM) along with in vitro and in vivo antioxidant as well as acetylcholinesterase (AChE) inhibition studies. Molecular docking studies were also performed for evaluation of molecular interaction of existed phenolic compounds in BFTP. In vitro antioxidant study revealed concentration dependant strong ability of BFTP to inhibit free radicals. In vitro AChE inhibition study showed competitive type of inhibition kinetics. BFTP significantly reversed (p < 0.005 versus scopolamine) the damaging effect of scopolamine by reducing TL (Transfer Latency) and TRC (Time taken to recognize the reward chamber) in the EPM and HWM, respectively. BFTP also contributed towards increased (p < 0.005 versus scopolamine) enzymatic antioxidant as well as hippocampal acetylcholine (ACh) levels. Histological studies also supported the results as BFTP pretreated mice significantly reversed the scopolamine induced histological changes in hippocampal region. Docking studies confirmed chlorogenic acid has the most significant binding affinity towards AChE. This research finding concludes that BFTP could be a beneficial agent for management of cognition and behavioral disorders associated with AD.

Molecular Pathogenesis, Organ Metastasis, and Targeted Therapy for Non-Small-Cell Lung Cancer.

Around 2 million people are diagnosed with lung cancer annually, causing 20,000 deaths. Non-small cell carcinomas account for 80-85% of lung cancer cases. Over the last few decades, there has been an improved understanding of the chromosomal makeup of lung cancer. As a result, the clinical care and treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC) have changed. This is possible due to advanced molecular techniques and chromosomal analysis, which have revealed persistent genetic abnormalities. Specific medications have increased the median survival time for NSCLC patients. Pulmonary pathology and oncology patients now receive personalized medication based on genetic abnormalities and other prognostic indicators. However, the diagnosis algorithms become complicated due to the various testing methods available. Consensus standards and recommendations have standardized NSCLC diagnostic testing. This article discusses the molecular genetic landscape of NSCLC and the latest therapy developments, focusing on clinically relevant changes using several schematic and tabular representations.

Solid Lipid Nanoparticles: A Review of their Biomedical Applications and Preparation.

Solid lipid nanoparticles (SLNs) are gaining significant attention in the pharmaceutical industry due to their biocompatibility and biodegradability, making them a popular functional nanocarrier. SLNs are a popular nanocarrier due to their ability to bypass the spleen and liver, offer high drug stability, and improve bioavailability, sterilization, immobilization, targeted drug release, and biocompatible ingredients. This article discusses various SLN preparation techniques, including high shear homogenization, hot homogenization, cold homogenization, microemulsion-based, solvent evaporation, solvent emulsification-evaporation, supercritical fluid-based, spray drying, double emulsion, and precipitation techniques, focusing on methodological aspects. This review discusses the physicochemical behavior of SLNs, including drug loading, release, particle size, stability, cytotoxicity, and cellular uptake, and their major biomedical applications.

Micelle confined mechanistic pathway for 4-nitrophenol reduction.

The model 4-nitrophenol reduction has been carried out by different groups in presence of metallic or even non-metallic catalyst elaborating different mechanistic aspects. In the present investigation, we have thoroughly studied the hydrogenation of 4-nitrophenol in a completely metal free homogeneous condition. The introduction of a non-fluorescent probe unequivocally generates a fluorescent molecule that indirectly justifies the anion radical stabilization in the micelle. The reduction mechanism under metal-free condition was proposed and the concept of stabilization of anion radical transition state of 4-nitrophenol at the positively charged Stern layer of anionic micelle was established. The plausible reduction mechanism has also enlightened the graphene-like conducting property of Stern layer of the homogeneous micellar system. Furthermore, the confinement effect for catalysis has also been authenticated by supporting experimental evidences. The borrowed concept of catalysis in confinement drives the catalytic study to a new era of catalysis.