Re(I)[2-aryl-1H-imidazo[4,5-f][1,10]phenanthroline] tricarbonyl chloride complexes for selective cancer therapy via a potential DNA damage mechanism.

Recently, achieving selective cancer therapy with trifling side effects has been a great challenge in the eradication of cancer. Thus, to amplify the cytoselective approach of complexes, herein, we developed a series of Re(I)[2-aryl-1H-imidazo[4,5-f][1,10]phenanthroline] tricarbonyl chloride complexes and screened their potency against HeLa and MCF-7 cell lines together with the evaluation of their toxicity towards a normal kidney cell line (HEK-293). On meticulous investigation, complex [ReI(CO)3Cl(K2-N,N-(2c))] (3c) was found to be the most potent anticancer entity among other complexes. Complex 3c also showed competency to induce apoptosis in MCF-7 cells through G2/M phase cell-cycle arrest in association with the generation of ample reactive oxygen species (ROS), eventually leading to DNA intercalation and internucleosomal cleavage. The order of the cytotoxicity of these complexes depended on their lipophilic character and the electron-withdrawing halogen substitution at the para-position of the phenyl ring in the imidazophenanthroline ligand.

GSH resistant, luminescent 2-(pyren-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline-based Ru(II)/Ir(III)/Re(I) complexes for phototoxicity in triple-negative breast cancer cells.

Selective chemotherapeutic strategies necessitate the emergence of a photosensitive scaffold to abate the nuisance of cancer. In the current context, photo-activated chemotherapy (PACT) has, therefore, appeared to be very effective to vanquish the vehemence of triple-negative breast cancer (TNBC). Metal complexes have been identified to act well against cancer cell microenvironment (high GSH content, low pH, and hypoxia), and thus they have been employed in the treatment of various types of cancer. As TNBC is very challenging to treat owing to its poor prognosis, lack of a specific target, high chance of relapse, and strong metastatic ability, herein we have aspired to design GSH-resistant phototoxic Ru(II)/Ir(III)/Re(I) based pyrene imidazophenathroline complexes to selectively avert the triple-negative breast cancer. The application of complexes, [RuL], [IrL], and [ReL] in the absence and in the presence of GSH against MDA-MB-231TNBC cells, has revealed that they are very active upon irradiation of visible light compared to dark due to the creation of copious singlet oxygen (1O2) as reactive oxygen species (ROS). Among three synthesized complexes, [IrL] has shown outstanding potency (IC50 = 3.70 in the absence of GSH and IC50 = 3.90 in the presence of GSH). Also, the complex, [IrL] is capable of interacting with DNA with the highest binding constant (Kb = 0.023 × 106 M-1) along with higher protein binding affinity (KBSA = 0.0321 × 106 M-1). Here, it has been unveiled that all the complexes have been entitled to involve DNA covalent interaction through the available sites of both adenine and guanine bases.

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.

The inclusion of diagnostics in national health insurance schemes in Cambodia, India, Indonesia, Nepal, Pakistan, Philippines and Viet Nam.

The Lancet Commission on Diagnostics highlighted a huge gap in access to diagnostic testing even for basic tests, particularly at the primary care level, and emphasised the need for countries to include diagnostics as part of their universal health coverage benefits packages. Despite the poor state of diagnostic-related services in low-income and middle-income countries (LMICs), little is known about the extent to which diagnostics are included in the health benefit packages. We conducted an analysis of seven Asian LMICs-Cambodia, India, Indonesia, Nepal, Pakistan, Philippines, Viet Nam-to understand this issue. We conducted a targeted review of relevant literature and applied a health financing framework to analyse the benefit packages available in each government-sponsored scheme. We found considerable heterogeneity in country approaches to diagnostics. Of the seven countries, only India has developed a national essential diagnostics list. No country presented a clear policy rationale on the inclusion of diagnostics in their scheme and the level of detail on the specific diagnostics which are covered under the schemes was also generally lacking. Government-sponsored insurance expansion in the eligible populations has reduced the out-of-pocket health payment burden in many of the countries but overall, there is a lack of access, availability and affordability for diagnostic-related services.

Accuracy of package inserts of SARS-CoV-2 rapid antigen tests: a secondary analysis of manufacturer versus systematic review data.

BACKGROUND: Rapid antigen tests (RATs) were crucial during the COVID-19 pandemic. Information provided by the test manufacturer in product package inserts, also known as instructions for use (IFUs), is often the only data available to clinicians, public health professionals, and individuals on the diagnostic accuracy of these tests. We aimed to assess whether manufacturer IFU accuracy data aligned with evidence from independent research. METHODS: We searched company websites for package inserts for RATs that were included in the July 2022 update of the Cochrane meta-analysis of SARS-CoV-2 RATs, which served as a benchmark for research evidence. We fitted bivariate hierarchical models to obtain absolute differences in sensitivity and specificity between IFU and Cochrane Review estimates for each test, as well as overall combined differences. FINDINGS: We found 22 (100%) of 22 IFUs of the RATs included in the Cochrane Review. IFUs for 12 (55%) of 22 RATs reported statistically significantly higher sensitivity estimates than the Cochrane Review, and none reported lower estimates. The mean difference between IFU and Cochrane Review sensitivity estimates across tests was 12·0% (95% CI 7·5-16·6). IFUs in three (14%) of 22 diagnostic tests had significantly higher specificity estimates than the Cochrane Review and two (9%) of 22 had lower estimates. The mean difference between IFU and Cochrane Review specificity estimates across tests was 0·3% (95% CI 0·1-0·5). If 100 people with SARS-CoV-2 infection were tested with each of the tests in this study, on average 12 fewer people would be correctly diagnosed than is suggested by the package inserts. INTERPRETATION: Health professionals and the public should be aware that package inserts for SARS-CoV-2 RATs might provide an overly optimistic picture of the sensitivity of a test. Regulatory bodies should strengthen their requirements for the reporting of diagnostic accuracy data in package inserts and policy makers should demand independent validation data for decision making. FUNDING: None.