Quinazolines as potent and highly selective PDE5 inhibitors as potential therapeutics for male erectile dysfunction

Kim, Young Hoon; Choi, Hojin; Lee, Jaekwang; Hwang, In‐Chang; Moon, Seung Kee; Kim, Soo Jin; Lee, Hong Woo; Im, Dai Sig; Lee, Sung Sook; Ahn, Soon Kil; Kim, Sang Woong; Han, Cheol; Yoon, Jeong Hyeok; Lee, Kyung Joo; Choi, Nam Song

doi:10.1016/j.bmcl.2008.09.108

Cited by 27 publications

(6 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Demonstrate the mostly outstanding less binding energy (more binding energy values) in favor of the docking molecule candidates. Alongside by (1)(2)(3)(4)(5)(6)(7)(8) Ligands in order to be docked with the enzyme EGFR TK's and CDK'S, the substituted NO 2 and N(CH 3 ) 2 group with Quinazolinone of ligand (QSL2 and QSD3) produced the mainstream efficient at the center of high binding score of -9.0 kcal/mol and -8.7kcal/mol. Among, ligands of substituted Cl, OCH 3 assembly exibits greatest docked score of (QSL1-QSL4 )8.6kcal/mol and 8.7kcal/mol and remaining Substituted ligands all had good docking scores more than-7.0kcal/mol against EGFR and CDK'S enzymes.…”

Section: Discussionmentioning

confidence: 99%

“…The quinazolin-4(3H)-one compounds are of extensive medicinal magnitude as of their assorted biological tricks. It have been experiential which exibits like antiviral, anticancer, antibacterial, antifungal, antitubercular, anticoccidial, 1 anti-inflammatory and analgesics, antidepressant, anticonvulsant, antimalarial, antioxidant, antileishmanial, 2 neuroprotectivie, 3 obesity, 4 antihypertensive, 5 anti-H1-antihistaminic, 6 and antiprotozoal activities. 7 The quinazoline candidate is a central part in array of drugs for instance Gefitinib, 8 Nolatrexed, 9 CS 1101 (CAL 101), 10,11 Erlotinib, 12 Milciclib, 13,14 and Lapatinib 15 (Figure 1a-b).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vitro Antioxidant, Cytotoxicity Study on EAC Cell Line of Quinazolin-4(3H)-one Derivatives: Synthesis, Molecular Docking, in silico Drug Likeness

Kasimayan¹,

Nagarajan²,

Ramalingam³

et al. 2023

Ind. J. Pharm. Edu. Res.

View full text Add to dashboard Cite

The quinazolin-4(3)-one exist an important sort of therapeutic drug candidates which attain integer of biological actions. In this research intended on design, synthesis, and Drug likeness, screened their antioxidant by DPPH method, Cytotoxicity tumor cell line by EAC method. Materials and Methods: The existing amendment evaluated their antioxidant actions of quinazolin-4(3H)-one derivatives (1-8) using Assay of 2,2-diphenyl-1-picryl hydrazyl radical scavenging (DPPH) followed by in vitro cytotoxicity done with tryban blue exclusion technique by Ehrlich ascites carcinoma cells (QSL2 and QSD3). Molecular docking studies performed using PDB: 1M17, 2kw6 by PyRx virtual screening Autodock Vina and also software's like admit SAR, Pkcsm used for physiochemical studies and Pharmacokinetic prediction as well as structures of synthesized molecules inveterate with spectral scrutiny of IR, 1 H, 13 C NMR as well as Molecular mass. Results: Among (1-8) Ligands in order to be docked with the enzyme EGFR TK'sand CDK'S the substituted NO 2 and N(CH 3 ) 2 group with Quinazolin-4(3H)-one (QSL2 and QSD3) produced the typical effectual with in the middle of elevated requisite rate of -9.0 kcal/mol and -8.7kcal/ mol. The ligands contains of Cl, OCH 3 gathering exibits best docked score of (QSL1-QSL4)8.6kcal/ mol and 8.7kcal/mol and residual ligands all possess good docking scores more than-7.0kcal/mol against EGFR and CDK'S enzymes. Among all the selected compounds refusal violation exibits drug likeness properties. Conclusion: On the whole study showed to most of the compounds is appropriate action against antioxidant, tumor cell line of anticancer agents. Depending upon the docking scores and in vitro study, drug likeness properties of the composite be selected, also endorse in vivo study which may perhaps carry on beneficial enroute for broad better inhibitoryquinazolin-4(3H)-one derivatives.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vitro Antioxidant, Cytotoxicity Study on EAC Cell Line of Quinazolin-4(3H)-one Derivatives: Synthesis, Molecular Docking, in silico Drug Likeness

Kasimayan¹,

Nagarajan²,

Ramalingam³

et al. 2023

Ind. J. Pharm. Edu. Res.

View full text Add to dashboard Cite

show abstract

“…Few quinazoline derivatives ( 103a – c ) were evaluated for their activity as potent and highly selective PDE5 inhibitors to be employed for male erectile dysfunction [ 89 ] (see Scheme 70 ).…”

Section: Biological Importance Of Quinazoline Derivativesmentioning

confidence: 99%

Chemical Characteristics, Synthetic Methods, and Biological Potential of Quinazoline and Quinazolinone Derivatives

Asif

2014

International Journal of Medicinal Chemistry

126

View full text Add to dashboard Cite

The heterocyclic fused rings quinazoline and quinazolinone have drawn a huge consideration owing to their expanded applications in the field of pharmaceutical chemistry. Quinazoline and quinazolinone are reported for their diversified biological activities and compounds with different substitutions bring together to knowledge of a target with understanding of the molecule types that might interact with the target receptors. Quinazolines and quinazolinones are considered as an important chemical for the synthesis of various physiological significance and pharmacological utilized molecules. Quinazolines and quinazolinone are a large class of biologically active compounds that exhibited broad spectrum of biological activities such as anti-HIV, anticancer, antifungal, antibacterial, antimutagenic, anticoccidial, anticonvulsant, anti-inflammatory, antidepressant, antimalarial, antioxidant, antileukemic, and antileishmanial activities and other activities. Being considered as advantaged scaffold, the alteration is made with different substituent.

show abstract

“…Quinazoline containing compounds display a variety of pharmacological effects, including antifungal [21], antimalarial [22], and antihypertensive effects (Figure 1). Vasodilation properties have been observed [23], mediated via modulation of the alpha 1-adrenergic (α 1 ) receptor [24] and PDE-5 enzyme [25]. We recently reported the preparation and evaluation of N 2 , N 4 - diamino quinazoline analogues as inhibitors of the latter target [26].…”

Section: Introductionmentioning

confidence: 99%

Elucidation of Vasodilation Response and Structure Activity Relationships of N2,N4-Disubstituted Quinazoline 2,4-Diamines in a Rat Pulmonary Artery Model

et al. 2019

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) is a rare and progressive disease arising from various etiologies and pathogenesis. PAH decreases life expectancy due to pulmonary vascular remodeling, elevation of mean pulmonary arterial pressure, and ultimately progresses to heart failure. While clinical treatments are available to reduce the associated symptoms, a complete cure has yet to be found. Phosphodiesterase-5 (PDE-5) inhibition has been identified as a possible intervention point in PAH treatment. The functional vasodilation response to N2,N4-diamino quinazoline analogues with differing PDE-5 inhibitory activities and varying physicochemical properties were assessed in both endothelium-intact and denuded rat pulmonary arteries to gain greater insight into their mode of action. All analogues produced vasorelaxant effects with EC50s ranging from 0.58 ± 0.22 µM to ˃30 µM. It was observed that vasodilation response in intact vessels was highly correlated with that of denuded vessels. The ~10% drop in activity is consistent with a loss of the nitric oxide mediated cyclic guanosine monophosphate (NO/cGMP) pathway in the latter case. A moderate correlation between the vasodilation response and PDE-5 inhibitory activity in the intact vessels was observed. Experimental protocol using the alpha-adrenergic (α1) receptor agonist, phenylephrine (PE), was undertaken to assess whether quinazoline derivatives showed competitive behavior similar to the α1 receptor blocker, prazosin, itself a quinazoline derivative, or to the PDE-5 inhibitor, sildenafil. Competitive experiments with the α1-adrenergic receptor agonist point to quinazoline derivatives under investigation here act via PDE-5 inhibition and not the former. The pre-incubation of pulmonary arterial rings with quinazoline test compounds (10 μM) reduced the contractile response to PE around 40–60%. The most promising compound (9) possessed ~32 folds higher selectivity in terms of vasodilation to its mammalian A549 cell cytotoxicity. This study provides experi0 0mental basis for PDE-5 inhibition as the mode of action for vasodilation by N2,N4-diamino quinazoline analogues along with their safety studies that may be beneficial in the treatment of various cardiovascular pathologies.

show abstract

Quinazolines as potent and highly selective PDE5 inhibitors as potential therapeutics for male erectile dysfunction

Cited by 27 publications

References 27 publications

In vitro Antioxidant, Cytotoxicity Study on EAC Cell Line of Quinazolin-4(3H)-one Derivatives: Synthesis, Molecular Docking, in silico Drug Likeness

In vitro Antioxidant, Cytotoxicity Study on EAC Cell Line of Quinazolin-4(3H)-one Derivatives: Synthesis, Molecular Docking, in silico Drug Likeness

Chemical Characteristics, Synthetic Methods, and Biological Potential of Quinazoline and Quinazolinone Derivatives

Elucidation of Vasodilation Response and Structure Activity Relationships of N2,N4-Disubstituted Quinazoline 2,4-Diamines in a Rat Pulmonary Artery Model

Contact Info

Product

Resources

About