Biguanides: Species with versatile therapeutic applications

Kathuria, Deepika; Raul, Akshay D.; Wanjari, Pravin J.; Bharatam, Prasad V.

doi:10.1016/j.ejmech.2021.113378

Cited by 42 publications

(48 citation statements)

References 460 publications

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“…There are four synthesis routes for preparation of proguanil derivatives [ 18 ], we choose the route with highest yield and experimental feasibility as shown in Scheme 1 . Ten new compounds were successfully obtained and named 2C – 10C and 12C .…”

Section: Discussionmentioning

confidence: 99%

Synthesis, Anti-Proliferative Evaluation and Mechanism of 4-Trifluoro Methoxy Proguanil Derivatives with Various Carbon Chain Length

Cao

Luo

et al. 2021

Molecules

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Among the known biguanide drugs, proguanil has the best antiproliferative activity. In contrast, newly synthesized biguanide derivatives containing fluorine atoms have excellent biological activity, among which trifluoromethoxy compounds show the strongest ability. Preliminary work in our laboratory exhibited that n-heptyl containing proguanil derivatives on one alkyl chain side have better biological activity than those with a shorter carbon chain. However, the relationship between the length of the carbon chain and the activity of the compounds is unknown. In this study, we synthesized 10 new trifluoromethoxy-containing proguanil derivatives with various carbon chain lengths. The phenyl side is fixed as the trifluoromethoxy group with change of carbon chain length in alkyl chain side. It was found that the anti-cancer abilities of 5C–8C with n-pentyl to n-octyl groups was significantly better than that of proguanil in the five human cancer cell lines. The colony formation assay demonstrated that 6C–8C at 0.5 to 1.0 μM significantly inhibited the colony formation of human cancer cell lines, much stronger than that of proguanil. Pharmacologically, 8C activates AMPK, leading to inactivation of the mTOR/p70S6K/4EBP1 pathway. Thus, these novel compounds have a great potential for developing new anti-cancer candidates.

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Section: Discussionmentioning

confidence: 99%

Synthesis, Anti-Proliferative Evaluation and Mechanism of 4-Trifluoro Methoxy Proguanil Derivatives with Various Carbon Chain Length

Cao

Luo

et al. 2021

Molecules

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“…More speculatively, antiviral properties have been attributed to molecules containing a biguanide moiety, including metformin ( Kathuria et al, 2021 ). Indeed, metformin was used in the management of influenza in 1950 (when it was known as “flumamine”), 7 years before its entry into clinical use for type 2 diabetes ( Bailey et al, 2007 ).…”

Section: Metformin and Covid-19mentioning

confidence: 99%

Diabetes, Metformin and the Clinical Course of Covid-19: Outcomes, Mechanisms and Suggestions on the Therapeutic Use of Metformin

Bailey

Gwilt

2022

Front. Pharmacol.

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Objectives: Pre-existing or new diabetes confers an adverse prognosis in people with Covid-19. We reviewed the clinical literature on clinical outcomes in metformin-treated subjects presenting with Covid-19.Methods: Structured PubMed search: metformin AND [covid (ti) OR covid-19 (ti) OR covid19 (ti) OR coronavirus (ti) OR SARS-Cov2 (ti)], supplemented with another PubMed search: “diabetes AND [covid OR covid-19 OR covid19 OR coronavirus (i) OR SARS-Cov2 (ti)]” (limited to “Clinical Study”, “Clinical Trial”, “Controlled Clinical Trial”, “Meta-Analysis”, “Observational Study”, “Randomized Controlled Trial”, “Systematic Review”).Results: The effects of metformin on the clinical course of Covid-19 were evaluated in retrospective analyses: most noted improved clinical outcomes amongst type 2 diabetes patients treated with metformin at the time of hospitalisation with Covid-19 infection. These outcomes include reduced admission into intensive care and reduced mortality in subgroups with versus without metformin treatment.Conclusion: The pleiotropic actions of metformin associated with lower background cardiovascular risk may mediate some of these effects, for example reductions of insulin resistance, systemic inflammation and hypercoagulability. Modulation by metformin of the cell-surface ACE2 protein (a key binding target for SARS-CoV 2 spike protein) via the AMP kinase pathway may be involved. While pre-existing metformin treatment offers potentially beneficial effects and can be continued when Covid-19 infection is not severe, reports of increased acidosis and lactic acidosis in patients with more severe Covid-19 disease remind that metformin should be withdrawn in patients with hypoxaemia or acute renal disease. Prospective study of the clinical and metabolic effects of metformin in Covid-19 is warranted.

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“…Biguanides are known to have a wide variety of therapeutic indications. Among others they are used as antidiabetic, antimalarial, anticancer, antimicrobial and antiviral agents [ 6 ]. From all biguanides, most research has been done with metformin.…”

Section: Metforminmentioning

confidence: 99%

Metformin: A Narrative Review of Its Potential Benefits for Cardiovascular Disease, Cancer and Dementia

2022

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The biguanide metformin has been used as first-line therapy in type 2 diabetes mellitus (T2DM) treatment for several decades. In addition to its glucose-lowering properties and its prevention of weight gain, the landmark UK Prospective Diabetes Study (UKPDS) demonstrated cardioprotective properties in obese T2DM patients. Coupled with a favorable side effect profile and low cost, metformin has become the cornerstone in the treatment of T2DM worldwide. In addition, metformin is increasingly being investigated for its potential anticancer and neuroprotective properties both in T2DM patients and non-diabetic individuals. In the meantime, new drugs with powerful cardioprotective properties have been introduced and compete with metformin for its place in the treatment of T2DM. In this review we will discuss actual insights in the various working mechanisms of metformin and the evidence for its beneficial effects on (the prevention of) cardiovascular disease, cancer and dementia. In addition to observational evidence, emphasis is placed on randomized trials and recent meta-analyses to obtain an up-to-date overview of the use of metformin in clinical practice.

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Biguanides: Species with versatile therapeutic applications

Cited by 42 publications

References 460 publications

Synthesis, Anti-Proliferative Evaluation and Mechanism of 4-Trifluoro Methoxy Proguanil Derivatives with Various Carbon Chain Length

Synthesis, Anti-Proliferative Evaluation and Mechanism of 4-Trifluoro Methoxy Proguanil Derivatives with Various Carbon Chain Length

Diabetes, Metformin and the Clinical Course of Covid-19: Outcomes, Mechanisms and Suggestions on the Therapeutic Use of Metformin

Metformin: A Narrative Review of Its Potential Benefits for Cardiovascular Disease, Cancer and Dementia

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