Heterocyclic compounds as a magic bullet for diabetes mellitus: a review

Farwa, Umme; Raza, Muhammad Asam

doi:10.1039/d2ra02697j

Cited by 13 publications

(5 citation statements)

References 227 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Te core structures found in the 86 scafolds included O, N, and S-heterocycles comprising indole, thiazole, isochromene, acridine-1,9-dione, imidazoline-2,4-dione, isoindoline-1,3dion, pyrazolo[4,3-c]pyridine, pyrido [4,3,b]indole, and 1,38triazaspiro [4,5]dione. Te medicinal properties of these heterocycles have been reported for the treatment of cancer, leishmaniasis, diabetes mellitus, and malaria [65][66][67]. Among the ten best scoring scafolds (Supplementary Table 1) to dutasteride, CHEMBL337492 and CHEMBL583325 (Supplementary Table 1) which are epimers of each other with a bis-(trifuoromethyl)benzene moiety were found to show a similarity score of 0.6055 and 0.56708, respectively.…”

Section: Scafold Hoppingmentioning

confidence: 96%

Docking and Molecular Dynamics Identify Leads against 5 Alpha Reductase 2 for Benign Prostate Hyperplasia Treatment

Saah

Sakyi

Adu-Poku

et al. 2023

Journal of Chemistry

View full text Add to dashboard Cite

Steroid 5 alpha-reductase 2 (5αR-2) is a membrane-embedded protein that together with other isoforms plays a key role in the metabolism of steroids. This enzyme catalyzes the reduction of testosterone to the more potent ligand, dihydrotestosterone (DHT) in the prostate. Androgens, testosterone, and DHT play important roles in prostate growth, development, and function. At the same time, both testosterone and DHT have been implicated in the pathogenesis of benign prostate hyperplasia (BPH). Inhibition of the DHT formation, therefore, provides a therapeutic strategy that offers the possibility of preventing, delaying, or treating BPH. Currently, two steroidal drugs that inhibit 5αR-2, dutasteride and finasteride, have been approved for clinical use. These two come at a high cost and also portray undesirable sexual side effects which necessitate the need to find new chemotherapeutic alternatives for the disease. Based on the aforementioned, finasteride and dutasteride were subjected to scaffold hopping, fragment-based de novo design, molecular docking, and molecular dynamics simulations employing databases like ChEMBL, DrugBank, PubChem, ChemSpider, and Zinc15 in the identification of potential hits targeting 5αR-2. Altogether, ten novel compounds targeting 5αR-2 were identified with binding energies lower or comparable to finasteride and dutasteride, the main inhibitors for this target. Molecular docking and molecular dynamics simulations studies identify amino acid residues Glu57, Phe219, Phe223, and Leu224 to be critical for ligand binding and complex stability. The physicochemical and pharmacological profiling suggests the potential of the hit compounds to be drug-like and orally active. Similarly, the quality parameter assessments revealed the hits possess LELP greater than 3 implying their promise as lead-like molecules. The compounds A5, A9, and A10 were, respectively, predicted to treat prostate disorders with Pa (0.188, 0.361, and 0.270) and Pi (0.176, 0.050, and 0.093), while A8 and A9 were found to be associated with BPH treatment with Pa (0.09 and 0.127) and Pi (0.077 and 0.033), respectively. Structural similarity searches via DrugBank identified the drugs faropenem, acemetacin, estradiol valerate, and yohimbine to be useful for BPH treatment suggesting the de novo designed ligands as potential chemotherapeutic agents for treating this disease.

show abstract

Section: Scafold Hoppingmentioning

confidence: 96%

Docking and Molecular Dynamics Identify Leads against 5 Alpha Reductase 2 for Benign Prostate Hyperplasia Treatment

Saah

Sakyi

Adu-Poku

et al. 2023

Journal of Chemistry

View full text Add to dashboard Cite

show abstract

“…This measurement is higher than that originating from the annual fatality of HIV‐AIDS [44] . Indeed, diabetic patients face various health‐related complications such as peripheral vasculopathy, myocardial ischemia, and endothelial defect that in turn lead to major macrovascular complications such as hypertension [45] . These problems are responsible for premature mortality and prolonged diseases that are significantly increasing owing to industrialization advent, life expectancy, and obesity all over the world.…”

Section: Introductionmentioning

confidence: 99%

Biological Applications of The Newly Designed Phthalocyanine‐Modified Gold Nanorods

Öztürk,

Özdemir,

Giray

et al. 2024

ChemistrySelect

View full text Add to dashboard Cite

In this study, a new di‐substituted phthalonitrile derivative namely 2‐[2‐{(3,5‐bis (trifluoromethyl) phenyl) ethynyl}‐4,5 dicyanophenyl] malonate was synthesized. The cycloteramerization of the resultant compound in the presence of the related metal salts resulted in a number of metal {M=Co, Mn, and Lu} phthalocyanines. The newly synthesized macromolecules were used for the functionalization of gold nanorods. To study the effect of modification and metal ion on the biological properties of the gold nanorods, the biological features of the phthalocyanines, phthalocyanine‐gold nanorod conjugates, and gold nanorods were examined by performing different biological approaches. In this study, the anti‐diabetic activities of fluorinated phthalocyanines and their gold nanorod conjugates were examined for the first time using pancreatic alpha‐amylase. The antioxidant activities of the studied nano/structures were analyzed using 2,2‐diphenyl‐1‐picrylhydrazil (DPPH) radical scavenging assay. Their antimicrobial and antimicrobial photodynamic therapy activities (APDT) were investigated, as well. They exhibited good DNA cleavage activities. The highest biofilm inhibition activities were obtained 97.49 and 91.53 % for 200 mg/L of nanoconjugate (7) against S. aureus and P. aeruginosa, respectively. All the studied biological candidates also displayed effective microbial cell viability inhibition activities against E. coli.

show abstract

“…Pyrimidine-containing derivatives also exhibit extensive biological activity, including anticancer [ 14 ], antidiabetic [ 15 ], and antibacterial [ 16 ] activity. Many derivatives containing pyrimidine rings have been studied synthetically and investigated for diabetic mellitus [ 17 ]. The construction of a new molecule containing two or more pharmacological groups simultaneously, considered molecular hybridization [ 18 ], has been of interest to many researchers [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, molecular docking study and molecular dynamics simulation of new coumarin-pyrimidine hybrid compounds having anticancer and antidiabetic activity

et al. 2023

View full text Add to dashboard Cite

Coumarin-pyrimidine hybrid compounds were synthesized by condensation reaction of α,β-unsaturated ketones of 6-acetyl-5-hydroxy-4-methylcoumarin with guanidine. The reaction yields were of 42–62%. The antidiabetic and anticancer activities of these compounds were examined. These compounds displayed low toxicity to two cancer cell lines (including KB and HepG2 ones), but exhibited remarkably active against α-amylase with IC 50 values of 102.32 ± 1.15 μM to 249.52 ± 1.14 μM and against α-glucosidase with IC 50 values of 52.16 ± 1.12 μM to 184.52 ± 1.15 μM. Amongst these compounds, 6c was the best inhibitory activity against α-amylase, and 6f had the highest activity against α-glucosidase. The kinetics of inhibitor 6f was competitive α -glucosidase inhibitor property. ADMET predictions showed that almost all synthesized compounds exhibited drug-like activity. IFD and MD simulations were carried out on enzymes 4W93 and 5NN8 to elucidate inhibitory potential of 6c and 6f against tested enzymes. The binding free energy calculation by MM-GBSA approach showed that Coulomb, lipophilic and van der Waals energy terms are major contributors for the inhibitor binding. Molecular dynamics simulations in water solvent system were carried out for the 6f /5NN8 complex to elucidate the variability of active interactions between ligand 6f and active pockets of this enzyme. Graphical Abstract

show abstract

Heterocyclic compounds as a magic bullet for diabetes mellitus: a review

Abstract: Diabetes mellitus (DM) is a major metabolic disorder due to hyperglycemia, which is increasing all over the world.

Cited by 13 publications

References 227 publications

Docking and Molecular Dynamics Identify Leads against 5 Alpha Reductase 2 for Benign Prostate Hyperplasia Treatment

Docking and Molecular Dynamics Identify Leads against 5 Alpha Reductase 2 for Benign Prostate Hyperplasia Treatment

Biological Applications of The Newly Designed Phthalocyanine‐Modified Gold Nanorods

Design, synthesis, molecular docking study and molecular dynamics simulation of new coumarin-pyrimidine hybrid compounds having anticancer and antidiabetic activity

Contact Info

Product

Resources

About