Cancer is one of the major causes of worldwide human mortality. A wide range of cytotoxic drugs are available on the market, and several compounds are in different phases of clinical trials. Many ...studies suggest that these cytotoxic molecules are also associated with different types of adverse side effects; therefore researchers around the globe are involved in the development of more efficient and safer anticancer drugs. In recent years, quinazoline and its derivatives have been considered as a novel class of cancer chemotherapeutic agents that show promising activity against different tumors. The aim of this article is to comprehensively review and highlight the recent developments concerning the anticancer activity of quinazoline derivatives as well as offer perspectives on the development of novel quinazoline derivatives as anticancer agents in the near future.
Tamoxifen (ICI 46 474), trans-1-(4-β-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene, is the most commonly used drug for the treatment of estrogen receptor positive breast cancer and has been saving ...lives worldwide for the past four decades. Tamoxifen is considered a pioneering drug due to its ubiquitous use in both treatment and chemoprevention of breast cancer and also for research addressing novel selective estrogen receptor modulators (SERMs). Tamoxifen is cost effective, lifesaving, and devoid of major side effects in the majority of patients. The discovery of tamoxifen metabolites such as 4-hydroxy tamoxifen, N-desmethyl tamoxifen, and endoxifen has facilitated understanding of tamoxifen's and its metabolites' mechanisms of action in breast cancer therapy. Continuous efforts are being made by both industry and academia to synthesize novel tamoxifen derivatives in order to better understand the mechanism of this drug's action and to generate new agents with reduced side effects for many therapeutic targets. This review article comprises the tamoxifen derivatives reported in the literature in the last few years and we anticipate that it will assist medicinal chemists in the synthesis of novel and pharmacologically potent agents for various therapeutic targets.
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•Tamoxifen is a pioneering drug for the treatment of ER-positive breast cancer cells.•Tamoxifen derivatives exhibited promising activity for cancer in addition to demonstrating other therapeutic activities.•Recent literature concerning synthesized tamoxifen derivatives and their pharmacological activities is reviewed.•The tamoxifen scaffold is an attractive target for the drug development.•The review will be useful for researchers who are developing novel tamoxifen derivatives aimed at several targets.
Xanthones are a class of oxygen containing heterocyclic compounds with a broad range of biological activities, and they have prominent significance in the field of medicinal chemistry. Xanthone is an ...attractive scaffold for the design and development of new drugs due to its promising biological activities, primarily as anticancer, antimalarial, antimicrobial, anti-HIV, anticonvulsant, anticholinesterase, antioxidant, anti-inflammatory, and as inhibitors of several enzymes like α-glycosidase, topoisomerase, protein kinase, aromatase, etc. In this review, we have compiled and discussed recent developments on the pharmacological profile of synthetic xanthone derivatives for different therapeutic targets. The review highlights the therapeutic significance of xanthones and offers support in the development of new xanthone derivatives as therapeutic agents.
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•Xanthone displayed a broad spectrum of biological activities.•Recent literature on synthesized xanthone derivatives and their pharmacological activities is covered.•Diverse activities of xanthones (e.g., anticancer, antimicrobial, antimalarial) are stated.•The review provides the chemical structures of the most active compound of the corresponding xanthone derivatives.•Xanthone scaffold is an attractive target for drug development.
In this study we followed a new approach to analyze molecular substructures required for hERG channel blockade. We designed and synthesized 40 analogues of dofetilide (1), a potent hERG potassium ...channel blocker, and established structure–activity relationships (SAR) for their interaction with this important cardiotoxicity‐related off‐target. Structural modifications to dofetilide were made by diversifying the substituents on the phenyl rings and the protonated nitrogen and by varying the carbon chain length. The analogues were evaluated in a radioligand binding assay and SAR data were derived with the aim to specify structural features that give rise to hERG toxicity.
Warning signs: Chemical alerts to reduce hERG toxicity were discovered by design and synthesis of 40 dofetilide analogues. The analogues were evaluated in a radioligand binding assay and structure–activity relationships were derived. The results may underscore the chemical groups that should be avoided to reduce the risk of hERG toxicity in other compound series.
The unforeseen emergence of coronavirus disease 2019 (COVID-19), a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the Wuhan province of China in December 2019, subsequently its ...abrupt spread across the world has severely affected human life. In a short span of time, COVID-19 has sacked more than one million human lives and marked as a severe global pandemic, which is drastically accountable for the adverse effect directly to the human society, particularly the health care system and the economy. The unavailability of approved and effective drugs or vaccines against COVID-19 further created conditions more adverse and terrifying. To win the war against this pandemic within time there is a desperate need for the most adequate therapeutic treatment, which can be achieved by the collaborative research work among scientists worldwide. In continuation of our efforts to support the scientific community, a review has been presented which discusses the structure and the activity of numerous molecules exhibiting promising SARS-CoV-2 and other CoVs inhibition activities. Furthermore, this review offers an overview of the structure, a plausible mechanism of action of SARS-CoV-2, and crucial structural features substantial to inhibit the primary virus-based and host-based targets involved in SARS-CoV-2 treatment. We anticipate optimistically that this perspective will provide the reader and researcher’s better understanding regarding COVID-19 and pave the path in the direction of COVID-19 drug discovery and development paradigm.
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•The COVID-19 is spreading across the world and needs effective treatment immediately.•This review provides a comprehensive overview of the encouraging therapeutic agents against SARS-CoV-2.•Small molecules with promising activity against various SARS-CoV-2 targets are discussed.•The review highlights SARS-CoV-2 structure, mechanism of action, and activity of molecules having potential for COVID-19 treatment.
Aromatase, a cytochrome P450 enzyme complex present in breast tissues, plays a significant role in the biosynthesis of important endogenous estrogens from androgens. The source of estrogen production ...in breast cancer tissues is intra-tumoral aromatase, and inhibition of aromatase may inhibit the growth stimulation effect of estrogens in breast cancer tissues. Consequently, aromatase is considered a useful therapeutic target in the treatment and prevention of estrogen-dependent breast cancer. Recently, different natural products and synthetic compounds have been rapidly developed, studied, and evaluated for aromatase inhibitory activity. Aromatase inhibitors are classified into two categories on the basis of their chemical structures, i.e., steroidal and nonsteroidal aromatase inhibitors. This review highlights the synthetic steroidal and nonsteroidal aromatase inhibitors reported in the literature in the last few years and will aid medicinal chemists in the design and synthesis of novel and pharmacologically-potent aromatase inhibitors for the treatment of breast cancer.
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•Aromatase inhibitors are competitive inhibitors of the enzyme aromatase, involved in the biosynthesis of estrogen from androgen.•The recent development of steroidal and nonsteroidal aromatase inhibitors was reviewed.•This review provides a pharmacological profile of the most active compound of the corresponding series of derivatives.•Molecular structures and structure activity relationships have been discussed.•The review will be useful for development of novel aromatase inhibitors.
•This study introduced and empirically tested psychological empowerment as the explanatory mechanism for the relationship between agile practices and performance.•Empirical support was found for the ...psychological empowerment mediated relationships between team autonomy and innovative behaviour and agile communication and innovative behaviour. Innovative behaviour also affected project performance.•Agile practices of team diversity and incremental and iterative development were not found to have a valid relationship with psychological empowerment.•The empirical validation of agile practices as a source of empowerment and motivation for agile teams is a new finding in the literature which has strong implications for both the theory and practice.•This research has also established that the difference between motivated and amotivated project teams lies in the communication and team autonomy constructs.
This study draws on the literature on psychological empowerment to conceptualize agile practices as a source of intrinsic motivation that enables the agile teams to deliver innovative outcomes. Then, drawing on the resource based view of innovative projects, the innovative behaviour of agile teams is cast as a project capability that affects project performance. To test this original conceptualization, data was collected to find support for the hypothesized relationships between agile practices, psychological empowerment, innovative behaviour and project performance. The statistical results showed that the agile practices of team autonomy and agile communication contributed to psychological empowerment that led to the innovative behaviour of agile teams. The innovative behaviour also affected project performance. The empirical validation of agile practices as a source of empowerment and motivation for agile teams is a new finding in the literature which has strong implications for both the theory and practice.
A national language policy reflects how a state looks at the languages used by its people. It assigns certain roles to languages, and addresses the issues of language education and language of ...education. Pakistan, a multilingual country, has yet no language policy at national level. This absence of policy has caused many issues, including the medium of instruction (MoI). Since the country is currently developing a single national curriculum, its success largely depends on resolving the issue of the medium of instruction. the paper, motivated by the same issue, introduces the problem, then, after discussing some major linguistic challenges faced by the country, it spotlights the difference between the Constitution (1973) and the National Education Policy on the issue of MoI. The paper takes insights from Integrative Framework (Hornberger, 2006) of language planning and policy, and Stage Actor Model (Zhao & Baldauf, 2012), to discuss actor agency and their role in solving the problem. The paper proposes a late-exit transitional bilingual model to address the issue of MoI in the country. It concludes with recommendations for a well-framed national language policy capable to de-stigmatise the national language Urdu, to give due recognition to regional or autochthonous languages, and to provide clear guidelines about the MoI in the formal education system of the country.
An update on the transition metal complexes, including copper, gold, manganese, and cadmium, as potential proteasome inhibitors for cancer treatment.
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•This review covers the recent ...advances of transition metal complexes as potential proteasome inhibitors.•The article focusses on the copper, manganese, cadmium and gold complexes with promising proteasome inhibitory activity.•The structure and activity of the most potent transition metal complex of the series discussed.•Significant for the medicinal chemist in the development of novel transition metal complexes for cancer treatment.
The discovery of cisplatin, a platinum-based drug, was a major breakthrough in cancer treatment strategies. However, the toxicity and drug resistance associated with cisplatin regulated the drug discovery research towards the rationale development of metal-containing agents with more specific activity and less toxicity and mode of action different from cisplatin and its derivatives. Consequently, the ubiquitin–proteasome pathway (UPP) developed as a novel and encouraging cancer treatment target. The metal-based compounds bearing proteasome inhibitory activity explored extensively as one of the important cancer treatment strategies. The bortezomib, a boron- containing compound, approved by the FDA as a first proteasome inhibitor for cancer treatment. Undoubtedly, bortezomib treatment benefited several cancer patients, but it is also associated with serious side effects such as drug resistance and ineffectiveness against solid tumors. To overcome bortezomib drawbacks researchers made efforts to discover new and structurally diverse anti-proteasome agents. In the last few years, several potential metal-based complexes discovered as proteasome inhibitors with reduced toxicity and improved clinical effectiveness. This mini-review article delivers to the reader the current update on the proteasome inhibition activity of transition metal complexes of copper, manganese, cadmium and gold. The recently reported transition metal complexes are included with discussion on the structure and the activity of the most potent complex of the series. The ubiquitin–proteasome pathway inhibition emerged as a promising target in the treatment of cancer and further research effort is obligatory in this area.
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