Investigation of Piperidine Derivatives in Ex Vivo Models of Pain and Platelet Aggregation

Zafar Saeed Saify,Huma Rasheed,Nousheen Mushtaq,Mehrun Nisa,Shazia Haider,Afshan Naz,Kaniz Fizza Azhar,Ghulam Abbas Miana 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.11

Piperidine derivatives are known to exhibit analgesic activities and are likely to possess the ability to block the effects of prostaglandins through inhibition of downstream signaling pathways. The present study investigated the activity of five derivatives (PD2-6) of 4-(4'-bromophenyl)-4-piperidinol (PD1), against pain and platelet aggregation mediated by the release of prostaglandins and thromboxane A2, respectively. The results showed that compound PD1and its two phenacyl derivatives PD3 and PD5 exhibited a highly significant analgesic effect (p < 0.01), whereas PD4 and PD6 also showed significant activity. PD3, the most active analgesic compound when docked to the opioid receptor, had interactions between the oxygen of its nitro group and the amino group of ARG 573, indicating a distance of 1.2563 Å. The antiplatelet data showed that compound PD5 (4-(4'-bromo-phenyl)-4-hydroxy-1-[2-(2'',4''-dimethoxyphenyl)-2-oxo-ethyl]-piperidinium bromide) had an IC50 = 0.06 mM, which was the most active compound, whereas PD3 was the second most active compound against platelet aggregating factor-induced aggregation with an IC50 = 80 mM. Acetyl salicylic acid (IC50 = 150 μM) was used as a positive control.

The role of cuscutain-propeptide inhibitor in haustoria parasitism and enhanced resistance to dodder in transgenic alfalfa expressing this propeptide

Massoume Amini,Saify Nabiabad Haida,Ali Deljou 한국식물생명공학회 2018 Plant biotechnology reports Vol.12 No.3

Cuscutain is a cysteine protease produced by dodder (the most important weeds of alfalfa) that is essential for the development and penetration of the haustoria in host. The propeptide subunit of cuscutain has a specific inhibitory function and inhibits the enzymatic activity of the cuscutain. In this study, we introduced the gene encoding the propeptide segment of the cuscutain (signal peptide-less inhibitor) into alfalfa and investigated its roles in parasitism and the alfalfa resistance to C. reflexa. Results demonstrated that cuscutain is mainly expressed in haustoria and the expression of propeptide in transgenic alfalfa plants effectively inhibited cuscutain enzyme activity and consequently interrupted haustoria development at the pathogenic stage. Digitate cells of haustoria could not differentiate into the xylem and phloem hyphae in dodder grown on transgenic alfalfa. Dodder development on transgenic alfalfa lines showed an overall reduction in fecundity and vigor due to imperfect attachment of haustoria. Morphology, nodule development and biomass of transgenic plants indicate that the inhibitory transgene exhibits exquisite specificity for cuscutain enzyme and by expression of the inhibitor in transgenic plants, there was no obvious adverse effect on them. The increased development and growth of dodder-challenged alfalfa transgenic plants compared to controls, showed the efficacy of propeptide in dodder control.

Studies on the Effects of Piperidine Derivatives on Blood Pressure and Smooth Muscles Contractions

Saeed, M.,Saify, Z.S.,Gilani, A.H.,Iqbal, Z. The Pharmaceutical Society of Korea 1998 Archives of Pharmacal Research Vol.21 No.4

Ten substituted phenacyl derivatives of 4-hydroxypiperidine were synthesized and studied for their effects on the mean arterial blood pressure (MABP) in normotensive anaesthetized rats and smooth muscles contractions of isolated rabbit jejunum. Two derivatives caused fall in blood pressure at the dose of 10-20 mg/kg and one rise in blood pressure at the dose of 20 mg/kg. Two compounds exhibited biphasic response (hypotensive followed by hypertensive) and one gave triphasic response at 10 mg/kg dose. Rest of four derivatives were found devoid of any effect on mean arterial blood pressure up to the dose of 30 mg/kg. All the derivatives except two caused relaxant effect on the spontaneous contraction of rabbit jejunum at the dose range of 0.1 -2 mg/kg.

Host-synthesized cysteine protease-specific inhibitor disrupts Cuscuta campestris parasitism in tomato

Massoume Amini,Haidar Saify Nabiabad,Ali Deljou 한국식물생명공학회 2017 Plant biotechnology reports Vol.11 No.5

Dodder (Cuscuta campestris) is one of the most important pests of tomato causing severe losses in yield. Cuscutain is a pre-pro-protein produced by dodder that has a cysteine proteinase function essential for normal development of the haustoria and parasitism, which involves the secretion and activation of cuscutain cysteine protease in the host plant tissue. The propeptide subunit of this enzyme has an inhibitory function and restricts the enzymatic activity of cuscutain. Here, we transformed the inhibitory propeptide segment of this enzyme into tomato and examined the tomato resistance to C. campestris. We demonstrate the expression of inhibitory propeptide in transgenic plants and find that it effectively interrupted cuscutain enzyme activity and haustoria development at the endophytic stage. Mature haustoria infecting transgenic hosts showed defects in searching hyphae development and these structures were not elongate, and in most cases no functional haustoria were formed due to inhibitor expression in the transgenic plants after prehaustoria contact. Dodder grown on transgenic lines showed an overall reduction in vigor and fecundity due to defective attachment of haustoria. The increased growth of dodder-challenged transgenic plants relative to controls, demonstrates the efficacy of cysteine protease inhibition in parasite plant control.

Interaction study of molten uranium with multilayer SiC/Y2O3 and Mo/Y2O3 coated graphite

Sharma S.K.,Saify M.T.,Majumdar Sanjib,Mollick Palash K. 한국원자력학회 2023 Nuclear Engineering and Technology Vol.55 No.5

Graphite crucibles are used for melting uranium and its alloys in VIM furnace. Various coating materials namely Al2O3, ZrO2, MgO etc. are applied on the inner surface of the crucibles using paint brush or thermal spray technique to mitigate U-C interaction. These leads to significant amount of carbon pick-up in uranium. In this study, the attempts are made to develop multilayer coatings comprising of SiC/Y2O3 and Mo/Y2O3 on graphite to study the feasibility of minimizing U-C interaction. The parameters are optimized to prepare SiC coating of about 70mm thickness using CVD technique on graphite coupons and subsequently Y2O3 coating of about 250mm thickness using plasma spray technique. Molybdenum and Y2O3 layers were deposited using plasma spray technique with 70mm and 250mm thickness, respectively. Interaction studies of the coated graphite with molten uranium at 1450C for 20 min revealed that Y2O3 coating with SiC interlayer provides physical barrier for uranium-graphite interaction, however, this led to the physical separation of coating layer. Y2O3 coating with Mo interlayer provided superior barrier effect showing no degradation and the coatings remained intact after interaction tests. Therefore, the Mo/Y2O3 coating was found to be a promising solution for minimizing carbon pick-up during uranium/ uranium alloy melting

Synthesis and Smooth Muscle-Selective Relaxant Activity of a Piperidine Analogue: 1-(4'-Fluorophenacyl)-4-Hydroxy-4-Phenyl-Piperidinium Chloride

Taqvi, Syed Intasar Hussain,Ghayur, Muhammad Nabeel,Gilani, Anwarul Hassan,Saify, Zafar Saeed,Aftab, Mohammad Tariq The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.1

The antispasmodic and vasodilator activities of a newly synthesized piperidine derivative (1-(4'fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride) were studied in vitro. The test compound exhibited a dose-dependent relaxant effect on the spontaneous and $K^+$ (75 mM)-induced contractions of isolated rabbit jejunum with respective $EC_{50}$ values of 0.01 mM(0.01-0.02, 95% CI) and 0.30 mM (0.17-0.56). The $Ca^{++}$ channel blocking (CCB) activity was confirmed when the test compound (0.1-0.2 mM) shifted the $Ca^{++}$ dose-response curves to the right, similar to that produced by verapamil ($0.1-1.0{\mu}M$), a standard CCB. In the isolated rabbit aorta, the test compound showed a dose-dependent vasodilator effect on $K^+$ (75 mM)-induced contractions with an $EC_{50}$ value of 0.08 mM (0.02-0.26) while also suppressed the norepinephrine ($1{\mu}M$) control peak responses with $EC_{50}$ value of 0.08 mM (0.05-0.13, n=5). When tested in Langendorff perfused rabbit heart preparation, the test compound exhibited a negligible inhibitory effect on the rate or force of atrial and ventricular contractions when tested up to 5 mM. The results show smooth muscle-selective relaxant effect of the test compound on intestinal and vascular preparations mediated possibly via blockade of voltage and receptor-operated $Ca^{++}$ channels.

Synthesis and Smooth Muscle-Selective Relaxant Activity of a Piperidine Analogue: 1-(4'-Fluorophenacyl)-4-Hydroxy-4-Phenyl-Piperidinium Chloride

Syed Intasar Hussain Taqvi,Muhammad Nabeel Ghayur,Anwarul Hassan Gilani,Zafar Saeed Saify,Mohammad Tariq Aftab 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.1

The antispasmodic and vasodilator activities of a newly synthesized piperidine derivative (1-(4'- fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride) were studied in vitro. The test compound exhibited a dose-dependent relaxant effect on the spontaneous and K+ (75 mM)- induced contractions of isolated rabbit jejunum with respective EC50 values of 0.01 mM (0.01- 0.02, 95% CI) and 0.30 mM (0.17-0.56). The Ca++ channel blocking (CCB) activity was confirmed when the test compound (0.1-0.2 mM) shifted the Ca++ dose-response curves to the right, similar to that produced by verapamil (0.1-1.0 µM), a standard CCB. In the isolated rabbit aorta, the test compound showed a dose-dependent vasodilator effect on K+ (75 mM)- induced contractions with an EC50 value of 0.08 mM (0.02-0.26) while also suppressed the norepinephrine (1 µM) control peak responses with EC50 value of 0.08 mM (0.05-0.13, n=5). When tested in Langendorff perfused rabbit heart preparation, the test compound exhibited a negligible inhibitory effect on the rate or force of atrial and ventricular contractions when tested up to 5 mM. The results show smooth muscle-selective relaxant effect of the test compound on intestinal and vascular preparations mediated possibly via blockade of voltage and receptoroperated Ca++ channels.

Genetic Identity between Bhadawari and Murrah Breeds of Indian Buffaloes (Bubalus bubalis) Using RAPD-PCR

Saifi, H.W.,Bhushan, Bharat,Kumar, Sanjeev,Kumar, Pushpendra,Patra, B.N.,Sharma, Arjava Asian Australasian Association of Animal Productio 2004 Animal Bioscience Vol.17 No.5

Randomly Amplified Polymorphic DNA-Polymerase Chain Reaction (RAPD-PCR) analysis was carried out with a battery of 11 random decamer primers to study band frequency (BF), genetic identity index (I) and mean average percentage difference (MAPD) between Bhadawari and Murrah breeds of buffalo. The primers OPA04 and BG15 resolved a band of 460 bp, which was present only in animals of Bhadawari breed. Whereas, the primers OPA14, BG27 and BG28 produced Murrah specific fragments of sizes 730 bp and 1,230 bp, respectively. The estimate of genetic identity index was highest (0.845) with the primer OPA01 and the lowest (0.479) with the primer BG27. The genetic identity index pooled over the primers was 0.596${\pm}$0.037 between these two breeds. The highest MAPD estimate (53.9) between the two breeds was obtained with the primer BG27 and the lowest (14.3) with the primer OPA01. It might be concluded that the genetic identity index between these two breeds calculated on the basis of BF showed moderate level of genetic identity with the primers employed. MAPD calculated on the basis of uncommon bands also demonstrated lower to medium level of genetic difference between Bhadawari and Murrah breeds of buffalo.

Determinant Factors of Firm Risk - Using the Structural Equation Modeling Approach: Evidence from Indonesia

WULANDARI, Asih Marini,RAHAYU, Sri Mangesti,SAIFI, Muhammad,NUZULA, Nila Firdausi Korea Distribution Science Association 2022 The Journal of Asian Finance, Economics and Busine Vol.9 No.8

The purpose of this study was to determine the relationship between company risk and factors such as business size, ownership structure, and leverage. The study was conducted on 142 manufacturing sector companies listed on the Indonesia Stock Exchange from 2013 to 2018. The purposive sampling method was used to select the research sample. The sample size for this study was 21 different companies. The analytical approach uses Structural Equation Modeling (SEM) with WarpPLS. According to the findings of the investigation, the size of the company has a significant influence on both the amount of leverage the company uses and the amount of risk the company takes. The level of leverage is significantly influenced by the ownership structure. However, the ownership structure does not have a significant impact on the level of risk the company; rather, leverage has a big impact on the level of risk the company faces. The findings of this study are helpful to prospective investors in measuring the risk posed by the company to make judgments regarding investments. The findings of this study are also essential for management to consider while controlling the risk of the organization.

Cement Augmentation of Vertebral Compression Fractures May Be Safely Considered in the Very Elderly

Anoop R. Galivanche,Courtney Toombs,Murillo Adrados,Wyatt B. David,Rohil Malpani,Comron Saifi,Peter G. Whang,Jonathan N. Grauer,Arya G. Varthi 대한척추신경외과학회 2021 Neurospine Vol.18 No.1

Objective: The objective of the current study was to perform a retrospective review of a national database to assess the safety of cement augmentation for vertebral compression fractures in geriatric populations in varying age categories. Methods: The 2005–2016 National Surgical Quality Improvement Program databases were queried to identify patients undergoing kyphoplasty or vertebroplasty in the following age categories: 60–69, 70–79, 80–89, and 90+ years old. Demographic variables, comorbidity status, procedure type, provider specialty, inpatient/outpatient status, number of procedure levels, and periprocedure complications were compared between age categories using chi-square analysis. Multivariate logistic regressions controlling for patient and procedural variables were then performed to assess the relative periprocedure risks of adverse outcomes of patients in the different age categories relative to those who were 60–69 years old. Results: For the 60–69, 70–79, 80–89, and 90+ years old cohorts, 486, 822, 937, and 215 patients were identified, respectively. After controlling for patient and procedural variables, 30-day any adverse events, serious adverse events, reoperation, readmission, and mortality were not different for the respective age categories. Cases in the 80- to 89-year-old cohort were at increased risk of minor adverse events compared to cases in the 60- to 69-year-old cohort. Conclusion: As the population ages, cement augmentation is being considered as a treatment for vertebral compression fractures in increasingly older patients. These results suggest that even the very elderly may be appropriately considered for these procedures (level of evidence: 3).