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Triazole-based acetamides serve as important scaffolds for various pharmacologically active drugs. In the present work, structural hybrids of 1,2,4-triazole and acetamides were furnished by chemically modifying 2-(4-isobutylphenyl) propanoic acid (1). Target compounds 7a-f were produced in considerable yields (70-76%) by coupling the triazole of compound 1 with different electrophiles under different reaction conditions. These triazole-coupled acetamide derivatives were verified by physiochemical and spectroscopic (HRMS, FTIR, (CNMR)-C-13, and (HNMR)-H-1,) methods. The anti-liver carcinoma effects of all of the derivatives against a HepG2 cell line were investigated. Compound 7f, with two methyl moieties at the ortho-position, exhibited the highest anti-proliferative activity among all of the compounds with an IC50 value of 16.782 mu g/mL. 7f, the most effective anti-cancer molecule, also had a very low toxicity of 1.190.02%. Molecular docking demonstrates that all of the compounds, especially 7f, have exhibited excellent binding affinities of -176.749 kcal/mol and -170.066 kcal/mol to c-kit tyrosine kinase and protein kinase B, respectively. Compound 7f is recognized as the most suitable drug pharmacophore for the treatment of hepatocellular carcinoma.

Triazole-based acetamides serve as important scaffolds for various pharmacologically active drugs. In the present work, structural hybrids of 1,2,4-triazole and acetamides were furnished by chemically modifying 2-(4-isobutylphenyl) propanoic acid (1). Target compounds 7a-f were produced in considerable yields (70-76%) by coupling the triazole of compound 1 with different electrophiles under different reaction conditions. These triazole-coupled acetamide derivatives were verified by physiochemical and spectroscopic (HRMS, FTIR, (CNMR)-C-13, and (HNMR)-H-1,) methods. The anti-liver carcinoma effects of all of the derivatives against a HepG2 cell line were investigated. Compound 7f, with two methyl moieties at the ortho-position, exhibited the highest anti-proliferative activity among all of the compounds with an IC50 value of 16.782 mu g/mL. 7f, the most effective anti-cancer molecule, also had a very low toxicity of 1.190.02%. Molecular docking demonstrates that all of the compounds, especially 7f, have exhibited excellent binding affinities of -176.749 kcal/mol and -170.066 kcal/mol to c-kit tyrosine kinase and protein kinase B, respectively. Compound 7f is recognized as the most suitable drug pharmacophore for the treatment of hepatocellular carcinoma.

The development of an economical method for the synthesis of biologically active compounds was the major goal of this research. In the present study, we have reported the ultrasound-radiation-assisted synthesis of a series of novel N-substituted 1,2,4-triazole-2-thiol derivatives. The target compounds 6a-f were efficiently synthesized in significant yields (75-89%) by coupling 1,2,4-triazole of 2-(4-isobutylphenyl) propanoic acid 1 with different electrophiles using ultrasound radiation under different temperatures. The sonication process accelerated the rate of the reaction as well as yielded all derivatives compared to conventional methods. All derivatives were confirmed by spectroscopic (FTIR, (HNMR)-H-1, (CNMR)-C-13, HRMS) and physiochemical methods. All derivatives were further screened for their anticancer effects against the HepG2 cell line. Compound 6d containing two electron-donating methyl moieties demonstrated the most significant anti-proliferative activity with an IC50 value of 13.004 mu g/mL, while compound 6e showed the lowest potency with an IC50 value of 28.399 mu g/mL. The order of anticancer activity was found to be: 6d > 6b > 6f > 6a > 6c > 6e, respectively. The in silico modelling of all derivatives was performed against five different protein targets and the results were consistent with the biological activities. Ligand 6d showed the best binding affinity with the Protein Kinase B (Akt) pocket with the lowest increment G value of -176.152 kcal/mol. Compound 6d has been identified as a promising candidate for treatment of liver cancer.

The development of an economical method for the synthesis of biologically active compounds was the major goal of this research. In the present study, we have reported the ultrasound-radiation-assisted synthesis of a series of novel N-substituted 1,2,4-triazole-2-thiol derivatives. The target compounds 6a-f were efficiently synthesized in significant yields (75-89%) by coupling 1,2,4-triazole of 2-(4-isobutylphenyl) propanoic acid 1 with different electrophiles using ultrasound radiation under different temperatures. The sonication process accelerated the rate of the reaction as well as yielded all derivatives compared to conventional methods. All derivatives were confirmed by spectroscopic (FTIR, (HNMR)-H-1, (CNMR)-C-13, HRMS) and physiochemical methods. All derivatives were further screened for their anticancer effects against the HepG2 cell line. Compound 6d containing two electron-donating methyl moieties demonstrated the most significant anti-proliferative activity with an IC50 value of 13.004 mu g/mL, while compound 6e showed the lowest potency with an IC50 value of 28.399 mu g/mL. The order of anticancer activity was found to be: 6d > 6b > 6f > 6a > 6c > 6e, respectively. The in silico modelling of all derivatives was performed against five different protein targets and the results were consistent with the biological activities. Ligand 6d showed the best binding affinity with the Protein Kinase B (Akt) pocket with the lowest increment G value of -176.152 kcal/mol. Compound 6d has been identified as a promising candidate for treatment of liver cancer.

Objectives: Tramadol, an atypical opioid, is clinically efficacious in treating moderate to severe pain. The aim of current study was to find out the toxicological effects of tramadol exposure to pregnant rats and fetuses during the late phase of pregnancy. Methods: Wistar pregnant rats were exposed to 1.25, 2.5, or 5 mg/kg/day tramadol from 14th to 20th day of pregnancy. The same therapy was given to nonpregnant rats for 7 days. The body weight, oral glucose and lipid tolerance tests, and effect on complete blood parameters in both pregnant and nonpregnant rats were determined. On 20th day, maternal placentas were excised and weighed while fetuses were observed for any deformity and growth retardation. Oxidative stress biomarkers were estimated in the liver and kidney tissue homogenates of the pregnant and nonpregnant rats while the whole fetus homogenate was processed for the same. Moreover, histopathology of the liver and kidney of pregnant and nonpregnant rats were carried out. Results: Tramadol administration did not significantly alter the area under curve of the blood glucose and triglyceride levels in both the pregnant and nonpregnant rats. It reduced the live fetuses, placental weights, fetal length, and fetal weights. Tramadol treated pregnant rats showed significantly (p <.05) reduced red blood cells, hematocrit, hemoglobin, and platelets with reference to control group. Similarly, structural abnormalities and malfunctioning of the liver and kidney of pregnant rats were instituted; however, it did not affect the structural integrity of nonpregnant rats. A substantial (p <.001–.0001) altered glutathione and malondialdehyde levels in the fetuses, pregnant, and nonpregnant animals (tissue homogenates) at all dosage levels were indicative of tramadol induced oxidative stress. Furthermore, tramadol exposure resulted in more significant (p <.01–.001) alteration of lipid profile in the pregnant than the nonpregnant animals. Conclusion: Acquired results suggested

Objectives: Tramadol, an atypical opioid, is clinically efficacious in treating moderate to severe pain. The aim of current study was to find out the toxicological effects of tramadol exposure to pregnant rats and fetuses during the late phase of pregnancy. Methods: Wistar pregnant rats were exposed to 1.25, 2.5, or 5 mg/kg/day tramadol from 14th to 20th day of pregnancy. The same therapy was given to nonpregnant rats for 7 days. The body weight, oral glucose and lipid tolerance tests, and effect on complete blood parameters in both pregnant and nonpregnant rats were determined. On 20th day, maternal placentas were excised and weighed while fetuses were observed for any deformity and growth retardation. Oxidative stress biomarkers were estimated in the liver and kidney tissue homogenates of the pregnant and nonpregnant rats while the whole fetus homogenate was processed for the same. Moreover, histopathology of the liver and kidney of pregnant and nonpregnant rats were carried out. Results: Tramadol administration did not significantly alter the area under curve of the blood glucose and triglyceride levels in both the pregnant and nonpregnant rats. It reduced the live fetuses, placental weights, fetal length, and fetal weights. Tramadol treated pregnant rats showed significantly (p <.05) reduced red blood cells, hematocrit, hemoglobin, and platelets with reference to control group. Similarly, structural abnormalities and malfunctioning of the liver and kidney of pregnant rats were instituted; however, it did not affect the structural integrity of nonpregnant rats. A substantial (p <.001–.0001) altered glutathione and malondialdehyde levels in the fetuses, pregnant, and nonpregnant animals (tissue homogenates) at all dosage levels were indicative of tramadol induced oxidative stress. Furthermore, tramadol exposure resulted in more significant (p <.01–.001) alteration of lipid profile in the pregnant than the nonpregnant animals. Conclusion: Acquired results suggested

The study was intended to find in vitro antioxidant, cytotoxicity and safety profile of Polystichum braunii roots extracts and chemically characterise it by GC–MS and FTIR spectroscopy. Acute and sub-chronic (90-day oral repeated dose at 150, 300 and 600 mg/kg) toxicity studies of P. braunii methanol extract (PBME) were performed in Wistar rats by adopting OECD guidelines. The PBME exerted the highest in vitro antioxidant potential. There was no substantial change in blood parameters and body weight except a notable (p < 0.01) rise in ALT, ALP, MDA and HDL, and decrease in cholesterol and LDL (p < 0.05) in animals sub-chronically treated with PBME at 600 mg/kg dose. The IC50 in HepG2 was more than 1000 µg/ml. The GC–MS analysis revealed Pentadecanoic acid and 9,12-Octadecadienoic acid in PBME. The P. braunii might be safe in acute usage, however, monitoring of liver function tests should be carried out during long-term use.

The study was intended to find in vitro antioxidant, cytotoxicity and safety profile of Polystichum braunii roots extracts and chemically characterise it by GC–MS and FTIR spectroscopy. Acute and sub-chronic (90-day oral repeated dose at 150, 300 and 600 mg/kg) toxicity studies of P. braunii methanol extract (PBME) were performed in Wistar rats by adopting OECD guidelines. The PBME exerted the highest in vitro antioxidant potential. There was no substantial change in blood parameters and body weight except a notable (p < 0.01) rise in ALT, ALP, MDA and HDL, and decrease in cholesterol and LDL (p < 0.05) in animals sub-chronically treated with PBME at 600 mg/kg dose. The IC50 in HepG2 was more than 1000 µg/ml. The GC–MS analysis revealed Pentadecanoic acid and 9,12-Octadecadienoic acid in PBME. The P. braunii might be safe in acute usage, however, monitoring of liver function tests should be carried out during long-term use.

Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75μg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.

Dengue Fever or commonly known as Dengue, a mosquito-borne arboviral infection has emerged as havoc around the globe. Annually, about 50 million infections are reported, resulting in 22,000 deaths and almost 2.5 billion people are reported living at risk. Dengue infection is caused by Dengue Virus (DENV), which is a member of genus Flavivirus and comprised of ten proteins; three proteins, capsid (C), membrane (M), and envelope (E), play structural role and seven are identified as non-structural that direct DENV replication. Four distinct serotypes: DENV-1, DENV-2, DENV-3 and DENV-4 are transmitted via Aedes mosquitoes. Clinically, Dengue patients can be categorized into three groups according to WHO 2009 revised classification. Typical symptoms of dengue include: extreme fatigue; sudden fever (from 3-7 days), headache, joint, muscle, and back pain; vomiting and diarrhea, appetite loss; skin rash along minor bleeding. Aedes aegypti is geographically distributed in tropical areas and breeds in artificially filled water containers i.e. drums, tyres, flower vases plastic food containers, tin cans, etc. Due to four viral serotypes and non-availability of the model animal for dengue, producing vaccines is a challenging task. Thus, Dengue can be managed using various vector control strategies through physical, chemical and biological means.

Dengue Fever or commonly known as Dengue, a mosquito-borne arboviral infection has emerged as havoc around the globe. Annually, about 50 million infections are reported, resulting in 22,000 deaths and almost 2.5 billion people are reported living at risk. Dengue infection is caused by Dengue Virus (DENV), which is a member of genus Flavivirus and comprised of ten proteins; three proteins, capsid (C), membrane (M), and envelope (E), play structural role and seven are identified as non-structural that direct DENV replication. Four distinct serotypes: DENV-1, DENV-2, DENV-3 and DENV-4 are transmitted via Aedes mosquitoes. Clinically, Dengue patients can be categorized into three groups according to WHO 2009 revised classification. Typical symptoms of dengue include: extreme fatigue; sudden fever (from 3-7 days), headache, joint, muscle, and back pain; vomiting and diarrhea, appetite loss; skin rash along minor bleeding. Aedes aegypti is geographically distributed in tropical areas and breeds in artificially filled water containers i.e. drums, tyres, flower vases plastic food containers, tin cans, etc. Due to four viral serotypes and non-availability of the model animal for dengue, producing vaccines is a challenging task. Thus, Dengue can be managed using various vector control strategies through physical, chemical and biological means.