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      Current status of carbazole hybrids as anticancer agents

      , ,
      European Journal of Medicinal Chemistry
      Elsevier BV

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          Abstract

          The drug resistance and low specificity of current available chemotherapeutics to cancer cells are the main reasons responsible for the failure of cancer chemotherapy and remain dramatic challenges for cancer therapy, creating an urgent need to develop novel anticancer agents. Carbazole nucleus, widely distributed in nature, is a predominant feature of a vast array of biologically active compounds. Carbazole derivatives exhibited potential antiproliferative activity against different cancer cell lines by diverse mechanisms, inclusive of arrest cell cycle and induce apoptosis, and several anticancer agents are carbazole-based compounds. Thus, carbazole derivatives represent a fertile source for discovery of novel anticancer therapeutic agents. Over the past several years, a variety of carbazole hybrids have been developed as potential anticancer agents. The present review focuses on the recent progress, from 2016 until now, in knowledge on anticancer properties, structure-activity relationships and mechanisms of action of carbazole hybrids to provide a basis for development of relevant therapeutic agents.

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          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches.
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              Improvement of conventional anti-cancer drugs as new tools against multidrug resistant tumors

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                Author and article information

                Journal
                European Journal of Medicinal Chemistry
                European Journal of Medicinal Chemistry
                Elsevier BV
                02235234
                February 2022
                February 2022
                : 229
                : 113999
                Article
                10.1016/j.ejmech.2021.113999
                34838335
                0db770c7-5332-44e9-adff-5127f92d110e
                © 2022

                https://www.elsevier.com/tdm/userlicense/1.0/

                https://doi.org/10.15223/policy-017

                https://doi.org/10.15223/policy-037

                https://doi.org/10.15223/policy-012

                https://doi.org/10.15223/policy-029

                https://doi.org/10.15223/policy-004

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