Ghassan Shattat

Synthesis and anti-hyperlipidemic evaluation of N‑(benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide derivatives in Triton WR-1339-induced hyperlipidemic rats.

The lipid-lowering activity of a series of novel N-(benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide derivatives has been studied in Triton WR-1339-induced hyperlipidemia in rats. The test animals were divided into four groups: control, hyperlipidemic, compound + 4% DMSO [C1: N-(2-benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide (1), C2: N-(3-benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide (2), C3: N-(4-benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide (3)]-treated and bezafibrate (BF)-treated. At a dose of 15 mg/Kg body weight, compounds 2, 3 and BF significantly reduced elevated plasma triglycerodes levels after 12 h. Moreover, high density lipoprotein-cholesterol levels were significantly increased in all treated groups after 12 h compared to the hyperlipidemic control group, except for C1 which was inactive. In sum, it may be stated that the results of the present study demonstrated new properties of some N-(benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide derivatives as potent lipid lowering agents and these beneficial activities may contribute to their cardioprotective and antiatherosclerotic role.

The hypolipidemic activity of novel benzofuran-2- carboxamide derivatives in Triton WR-1339-induced hyperlipidemic rats: a comparison with bezafibrate

Using Triton WR-1339-induced hyperlipidemic rats as an experimental model, we investigated whether compound 4 [N-(9,10-dihydro-9,10-dioxoanthracen-2-yl)bezofuran-2-carboxamide] and compound 5 [N-(4-benzoylphenyl)benzofuran-2-carboxamide], two novel anti-hyperlipidemic agents, have any effect on plasma triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol levels (HDL-C) levels. The tested animals were divided into control (CG), hyperlipidemic (HG), and compounds 4, 5, and bezafibrate (BF) treated groups. At a dose of 15 mg/kg body weight, compounds 4, 5, and BF significantly reduced elevated plasma TG levels after 7 and 24 h. Furthermore, HDL-C levels were remarkably increased in all treated groups after 7 and 24 h compared to the hyperlipidemic control group. However, only compounds 4 and 5 treated groups clearly showed a significant reduction in plasma total cholesterol levels after 7 and 24 h. It is therefore reasonable to assume that compounds 4 and 5 may have promising potential in the treatment of hyperlipidemia and atherosclerosis.

In Vivo Antihyperlipidemic Activity of a New Series of N‐(Benzoylphenyl) and N‐(Acetylphenyl)‐1‐benzofuran‐2‐carboxamides in Rats

A new series of N‐(benzoylphenyl) and N‐(acetylphenyl)‐1‐benzofuran‐2‐carboxamides (3a–3d and 4a′–4c′) were synthesized. Compounds (3a, 3b, and 4a′–4c′) were tested in vivo using Triton‐WR‐1339‐induced hyperlipidemic rats as an experimental model for their hypolipidemic activity. The tested animals were divided into eight groups: control, hyperlipidemic, 3a, 3b, 4a′, 4b′, 4c′, and bezafibrate. At a dose of 15 mg/kg, the elevated plasma triglyceride (TG) levels were significantly reduced in compounds 3b (p <0.0001) and 4c′ (p <0.05) after 12 and 24 h compared to the normal control group. Furthermore, high‐density lipoprotein‐cholesterol levels were remarkably increased in compounds 3b (p <0.001) and 4c′ (p <0.05). Meanwhile, compound 4b′ slightly reduced the TG levels after 12 and 24 h. The present study demonstrated new properties of the novel series of benzofuran‐2‐carboxamides 3b and 4c′ as potent lipid‐lowering agents. It is, therefore, reasonable to assume that compounds 3b and 4c′ may have a promising potential in the treatment of hyperlipidemia and coronary heart diseases.

Antihyperlipidemic Properties of Novel N-(Benzoylphenyl)-5-substituted-1H-indole-2-carboxamides in Triton WR-1339-Induced Hyperlipidemic Rats

In the search for new potential antihyperlipidemic agents, the present study focuses on the synthesis of novel N-(benzoylphenyl)-5-substituted-1H-indole-2-carboxamides (compounds 8-12, 15, 16, 18) and investigating their antihyperlipidemic activity using Triton WR-1339-induced hyperlipidemic rats as an experimental model. Hyperlipidemia was developed by intraperitoneal injection of Triton WR-1339 (250 mg/kg body weight). The tested animals were divided into normal control (NCG), hyperlipidemic (HG), compound 8, 9, 15, 16, 18- and bezafibrate treated groups. At a dose of 15 mg/kg body weight, compounds 9, 16, 18 and bezafibrate (100 mg/kg) significantly (p < 0.0001) reduced elevated plasma triglycerides levels after 12 h compared to the hyperlipidemic control group. However, only the group treated with compounds 9, 16 and 18 showed an obviously significant (p < 0.001) reduction in plasma total cholesterol levels after 12 h compared to the hyperlipidemic control group. Moreover, high density lipoprotein-cholesterol levels were significantly (p < 0.0001) increased in all treated groups after 12 h compared to the hyperlipidemic control group, except for compounds 8 and 15 which revealed inactive. It is therefore reasonable to assume that compounds 9, 16 and 18 may have potential in the treatment of hyperlipidemia.

Pharmacological evaluation of novel indole-2-carboxamides as potent lipid-lowering agents in Triton-WR-1339-induced hyperlipidemic rats.

The lipid-lowering effects of two novel antihyperlipidemic agents, BMI2C [N-(4-benzoylphenyl)- 5-methoxy-1H-indole-2-carboxamide] and DDMI2C [N-(9,10-dihydro-9,10-dioxoanthracen- 2-yl)-5-methoxy-1H-indole-2-carboxamide], were studied using hyperlipidemic rats as an experimental model; hyperlipidemia was developed by intraperitoneal injection of Triton WR-1339 (200 mg/kg body weight). At a dose of 15 mg/kg body weight, BMI2C and DDMI2C signifi cantly reduced elevated plasma triglyceride levels after 7 and 24 h. Furthermore, BMI2C and DDMI2C significantly reduced elevated plasma total cholesterol levels after 24 h. Interestingly, high-density lipoprotein-cholesterol levels were significantly increased in all treated groups. These findings indicate that the two studied novel compounds have a promising potential in the treatment of hyperlipidemia and atherosclerosis

Blood Pressure, Heart Rate, and CNS Stimulant Medication Use in Children with and without ADHD: Analysis of NHANES Data

It is estimated that 2–3% of children in the US have hypertension (HTN) and 8% of children ages 4–17 carry the diagnosis of attention-deficit hyperactivity disorder (ADHD). The prevalence of HTN and cardiovascular (CV) risk factors in children with ADHD on CNS stimulant treatment (stimulants) compared to no treatment and compared to their healthy counterparts is not well described. Using National Health and Nutrition Survey data, we examined demographic, blood pressure (BP) and CV risk factors of 4,907 children aged 12–18 years with and without the diagnosis of ADHD, and further examined the CV risk in a subgroup of ADHD patients on stimulants. Three hundred eighty-three (10.7%) children were reported to have ADHD, of whom 111 (3.4%) were on stimulants. Children with ADHD on stimulants were significantly younger, male, and white compared to those with ADHD not on medication and those without ADHD. Body mass index (BMI), eGFR, cholesterol, the prevalence of albuminuria, and poverty were not significantly different between the three groups. One hundred sixty (2.7%) had BP in the hypertensive and 637 (12.4%) in the pre-hypertensive range. The prevalence of elevated BP (HTN and/or pre-HTN range) was not different between children with ADHD on stimulants compared to ADHD without medication and those without ADHD. Heart rate (HR) was significantly higher in the ADHD group on stimulants vs. the groups ADHD on no stimulants and without ADHD. When the relationship between stimulants and the risk of abnormal BP was examined, there was a significant interaction between having BP in the HTN range and sex. After adjusting for BMI, race, and age, females with ADHD on stimulants tended to be older and had significantly more BP in the hypertensive range. On the other hand, males were more likely to be of a white race and older, but not hypertensive. Children with ADHD on stimulants have significantly higher HR than children with ADHD on no stimulants and children without ADHD. On the other hand, the prevalence of abnormal BP classification is comparable between the three groups.

Synthesis and Pharmacological Evaluation of Novel Substituted and Unsubstituted N-(Benzoylphenyl)-1H-indole-2-carboxamides as Potent Antihypertriglyceridemic Agents

The N-(benzoylphenyl)-1H-indole-2-carboxamide derivatives 1 - 6 were synthesized, and the lipid-lowering effects of two of these novel compounds were studied using hyperlipidemic rats as an experimental model. Treatment of ethyl-1H-indole-2-carboxylate with aminobenzophenones in the presence of sodium ethoxide and DMF, followed by purifi cation using column chromatography, gave the target compounds in good yields. The tested animals were divided into control, hyperlipidemic, compounds 2-, 3- and bezafibrate-treated groups. At a dose of 15 mg/kg body weight, compounds 2, 3 and bezafibrate significantly reduced the elevated plasma triglyceride levels after 7 and 24 h. Furthermore, the high-density lipoprotein- cholesterol levels were remarkably increased in all treated groups after 7 and 24 h compared to the hyperlipidemic control group. However, only compounds 2- and 3-treated groups obviously showed a significant reduction in plasma total cholesterol levels after 24 h. It is therefore reasonable to assume that 2 and 3 may have a promising potential in the treatment of hyperlipidemia and coronary heart diseases.

Synthesis and antibacterial properties of new N4-acetylated hexahydro-2,7-dioxopyrido[2,3-f]quinoxaline-8-carboxylic acids

Direct interaction between 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid and primary α-amino acids (exemplified by glycine, alanine, and l-valine) in aqueous ethanolic NaHCO3 at 70–80°C for 24–72 h produced the respective N-(4-oxoquinolin-7-yl)-α-amino acids (6a–c). The latter derivatives underwent reductive lactamization upon treatment with Na2S2O4 in aqueous ethanol to afford moderate yields of the corresponding pyrido[2,3-f]quinoxaline-8-carboxylic acids (8a–c). Acetylation of 8a–c using acetyl chloride afforded N4-acetylated hexahydro-2,7-dioxopyrido[2,3-f]quinoxaline-8-carboxylic acids (9a–c). The structures, assigned to these new heterocyclic products, are supported by analytical and spectral data. The synthesized compounds (6a–c/9a–c) showed appreciable antibacterial activity as compared with ciprofloxacin.

Synthesis of Novel N-(4-benzoylphenyl)-2-furamide Derivatives and their Pharmacological Evaluation as Potent Antihyperlipidemic Agents in Rats

In the search for new potential antihyperlipidemic agents, the present study focuses on the synthesis and pharmacological activity of a series of novel N-(4-benzoylphenyl)-2-furamides (3a-3e). Hyperlipidemia was induced in rats by single intraperitoneal injection of Triton WR-1339 (300 mg/kg body weight). At a dose of 15 mg/kg body weight, compounds 3b, 3d and bezafibrate (100 mg/kg) significantly (p<0.0001) reduced elevated plasma triglyceride levels after 18 h compared to the hyperlipidemic control group. However, only groups treated with compounds 3b, and 3d obviously showed a significant (p<0.0001) reduction in plasma total cholesterol levels. Moreover, high density lipoprotein-cholesterol levels were significantly (p<0.0001) increased in animals treated with compounds 3b, 3d and bezafibrate. It is therefore reasonable to assume that compounds 3b and 3d may have promising potential in the treatment of hyperlipidemia. This beneficial activity may contribute to their cardioprotective and antiatherosclerotic role.

The pharmacological effects of novel 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamide derivatives on plasma lipid profile of Triton-WR-1339-induced Wistar rats.

A novel series of 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamides (3c–3g) were synthesized. The present study was undertaken to investigate the possible antihyperlipidemic effect of these novel compounds on hyperlipidemic rats. Hyperlipidemia was induced by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg). The tested animals were divided into normal control (NCG), hyperlipidemic control (HCG), compounds 3c-, 3d-, 3e-, 3f-, 3g- and bezafibrate (BF)-treated groups. At a dose of 15 mg/kg, compounds 3c–3g and BF (100 mg/kg) significantly (p < 0.0001) reduced elevated plasma triglycerides levels after 12 and 24 h compared to the hyperlipidemic control group. However, only compounds 3e and 3g obviously showed a significant (p < 0.0001) reduction in plasma total cholesterol levels after 12 and 24 h. Moreover, high-density lipoprotein cholesterol levels were significantly increased in all treated groups. The current study demonstrates that 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamides (3c–3g) have a definite antihyperlipidemic potential and these beneficial activities may contribute to their cardioprotective and antiatherosclerotic role.