Muhammad Naveed Umar

Nanobiotechnology and its applications in drug delivery system: a review

Nanobiotechnology holds great potential in various regimes of life sciences. In this review, the potential applications of nanobiotechnology in various sectors of nanotechnologies, including nanomedicine and nanobiopharmaceuticals, are highlighted. To overcome the problems associated with drug delivery, nanotechnology has gained increasing interest in recent years. Nanosystems with different biological properties and compositions have been extensively investigated for drug delivery applications. Nanoparticles fabricated through various techniques have elevated therapeutic efficacy, provided stability to the drugs and proved capable of targeting the cells and controlled release inside the cell. Polymeric nanoparticles have shown increased development and usage in drug delivery as well as in diagnostics in recent decades.

In-Plane Behavior of the Dhajji-Dewari Structural System (Wooden Braced Frame with Masonry Infill)

This paper presents experimental and numerical investigations conducted on typical dhajji buildings found in the northern mountainous areas of Kashmir and surrounding regions to evaluate their in-plane lateral load response. The experimental work included an in-plane quasistatic cyclic test on three full-scale walls as well as monotonic tension and bend tests on main connections. The test results show that the dhajji-dewari system of buildings possesses tremendous resilience against lateral forces. The function of connections, especially the connections between the vertical posts and bottom plate, control the performance of the system. The test results also indicate that although masonry infill does not contribute to lateral load capacity, it significantly increases the energy dissipation capacity of system. The data accrued from the tests has been used in nonlinear static push-over analysis of the numerical models to develop simplified analytical tools for facilitating lateral load performance evaluation of dhajji structures.

Synthesis and relaxivity measurement of porphyrin-based Magnetic Resonance Imaging (MRI) contrast agents

Magnetic Resonance Imaging (MRI) has become a prominent imaging technique in medicine. MRI contrast agents are used to increase the sensitivity of this technique. Recently, a new method for cancer treatment with a less side effect called photodynamic therapy (PDT) has been introduced. In this method cancer tissues are selectively destroyed without injuring the surrounding healthy cells. However, for the successful use of this method, the selection of an appropriate photosensitizer is important. Hence, diagnosis-treat union of MRI and PDT will be significantly promoted if a new family of bi-functional agents is found, which would combine the effects of a contrast agent in MRI and of a photosensitizer in PDT. It will bring great improvement to the cancer diagnosis and treatment. Porphyrins have proved to be useful photosensitizing agents in PDT due to their promising photophysical efficiency and a less side effect. This work briefly describes the research development of porphyrins as a photosensitizer applied in PDT, and also highlights the recent progress in the research on bi-functional agents of MRI-PDT. Diethylenetriamine pentaacetic acid (DTPA) units are incorporated at a meso-position of the porphyrin ring to synthesize new bi-functional agents of MRI-PDT with sufficient water solubility and high relaxation potency. Gd3+ complexes are prepared by the reaction of the high molecular weight porphyrin-based ligand with GdCl3·6H2O. The longitudinal relaxivity measurement indicates 154% and 251% enhancement compared to that of the widely used MRI contrast agent Gd-DTPA. These results indicate that the two complexes could possibly be used as bi-functional agents of MRI-PDT.

Cyclen-based Gd(3+) complexes as MRI contrast agents: Relaxivity enhancement and ligand design.

Magnetic Resonance Imaging (MRI) is a noninvasive radiology technique used to examine the internal organs of human body. It is useful for the diagnosis of structural abnormalities in the body. Contrast agents are used to increase the sensitivity of this technique. 1,4,7,10-Tetraazacyclododecane (cyclen) is a macrocyclic tetraamine. Its derivatives act as useful ligands to produce stable complexes with Gd3+ ion. Such chelates are investigated as MRI contrast agents. Free Gd3+ ion is extremely toxic for in vivo use. Upon complexation with a cyclen-based ligand, it is trapped in the preformed central cavity of the ligand resulting in the formation of a highly stable Gd3+-chelate. Better kinetic and thermodynamic stability of cyclen-based MRI contrast agents decrease their potential toxicity for in vivo use. Consequently, such agents have proved to be safest for clinical applications. Relaxivity is the most important parameter used to measure the effectiveness of a contrast agent. A number of factors influence this parameter. This article elucidates detailed strategies to increase relaxivity of cyclen-based MRI contrast agents. 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) are two key ligands derived from cyclen. They also act as building blocks for the synthesis of novel ligands. A few important methodologies for the synthesis of DOTA and DO3A derivatives are described. Moreover, the coordination geometry of chelates formed by these ligands and their derivatives is discussed as well. Novel ligands can be developed by the appropriate derivatization of DOTA and DO3A. Gd3+-chelates of such ligands prove to be useful MRI contrast agents of enhanced relaxivity, greater stability, better clearance, lesser toxicity and higher water solubility.

Seismic Vulnerability Assessment of Multistory Timber Braced Frame Traditional Masonry Structures

Research carried out on the seismic investigation of timber braced frame (TBF) masonry structures of traditional construction practice is presented, essential for seismic performance evaluation of such construction type using engineering approaches. An innovative simplified equivalent frame method (EFM) based on macro modelling approach is presented for nonlinear dynamic seismic analysis of TBF masonry structures. The modelling include EFM idealization of wall using stiff elastic beam-column element assigned with moment-rotation (M-θ) nonlinear lumped plasticity hinges. Earlier, the approach i.e. the EFM idealization and M-θ constitutive law, is calibrated with the experimental results obtained through quasi-static cyclic test on full scale walls. The technique is further extended herein for seismic dynamic analysis of multistory structures. Generalization of the technique for modelling walls of various geometry and loading is performed. It included nonlinear static pushover analysis of various case study walls, by means of SAP2000 calibrated earlier with experimental results, for the derivation of lateral force-deformability behavior towards the development of generalized M-θ constitutive law for TBF masonry walls. Three representative structures, from one to three storeys, are analyzed using a suite of ten natural accelerograms and incremental dynamic analysis technique. Structure fragility and resilience functions are derived using a fully probabilistic and dynamic approach. The structures analyzed in the present study represent TBF masonry wall structures, called as Dhajji-Dewari structures, common in Northern areas of Pakistan.

Attenuation and Production of the Amphotericin B-Resistant Leishmania tropica Strain

Background Infections caused by Leishmania are becoming major public health problems on a global scale. Many species of Leishmania around the world are obtaining resistance levels of up to 15 folds, as estimated by the World Health Organization. Leishmania showing resistance is relatively difficult to observe and maintain in laboratory settings. Objectives The current study deals with the generation of Leishmania tropica strains that are resistant to amphotericin B (amp B). Materials and Methods The L. tropica strain was attenuated using continuous passaging 20 times. The infectivity of L. tropica was confirmed in BALB/c mice. The L. tropica resistant strain was produced in vitro using a continuous increase in drug pressure. The cross resistance of L. tropica to other drugs was also investigated. Results After 20 continuous passages, the BALB/c mice tested negative in the development of leishmaniasis. At a concentration of 0.1 µg/mL, L. tropica showed resistance to amp B. The newly developed promastigotes were 16 times more resistant compared to the resistance of the wild type promastigotes. The resistant L. tropica strain showed cross resistance to itraconazole and had a resistance index that was greater than five. The resistant strain displayed maximum stability for more than three months in the drug-free medium. Conclusions The resistant strain of L. tropica can be produced in laboratories using continuous drug pressure. The attenuated resistant strain has significant implications (both medically and academically) in the ability to overcome resistance.

FACILE SYNTHESIS, CHARACTERIZATION AND DFT CALCULATIONS OF 2-ACETYL PYRIDINE DERIVATIVES

Haroon ur Rashida, Adnan Shahzadb,d, Zarif Gulc, Ezzat Khanc,*, Muhammad Naveed Umarc,#, Muhammad Raza Shahd, Awal Noore and Sher Wali Khanf Department of Chemistry, Sarhad University of Science & Information Technology, Peshawar, Khyber Pakhtunkhwa, Pakistan Institute of Chemical Science, University of Swat, Swat, Khyber Pakhtunkhwa, Pakistan Department of Chemistry, University of Malakand, Chakdara, Dir (Lower), Khyber Pakhtunkhwa, Pakistan HEJ Research Institute, Sindh University, Karachi, Pakistan. Anorganishe Chemie II, Universität Bayreuth, D-95440 Bayreuth, Germany Department of Chemistry, Shaheed Benazir Bhutto University, Shringel, Upper Dir, Khyber Paktunkhwa, Pakistan

Synthesis and characterization of monoaryl esters of l -tartaric acid and their process for fries rearrangement

Chiral protected monoaryl esters (2a–2h) were synthesized from monoester of l-tartaric acid, having two asymmetric centers and C2 axis of symmetry. l-tartaric acid was protected and partially hydrolyzed to give the corresponding monoester. Monoester upon treatment with different substituted phenols gave desired monoaryl esters (2a–2h). Fries rearrangement of monoaryl esters was then tried under various conditions by using different Lewis acids. All the compounds were purified and characterized by using spectroscopic techniques like IR, 1H-NMR, 13C-NMR, HRMS-ESI, and elemental analysis. The structure of compound 2e was obtained by X-ray crystallography.

In Vitro Enzyme Inhibition Potentials and Antioxidant Activity of Synthetic Flavone Derivatives

Free radicals are produced by an important chemical process known as oxidation that in turn initiates chain reactions to damage the cells and originate oxidative stress. Flavones have got special position in research field of natural and synthetic organic chemistry due to their biological capabilities as antioxidant. The antioxidants are known to possess extensive biological effects that include antiviral, antibacterial, anti-inflammatory, antithrombotic, and vasodilatory activities. The simple flavone (F1) and substituted flavone derivatives (F2–F5) have been synthesized from o-hydroxyacetophenone and benzaldehyde derivatives in good yield. The structures have been established by different spectroscopic techniques like 1H NMR, 13C NMR, IR, and elemental analysis. Antioxidant profile of these compounds was established using DPPH and H2O2 free radical scavenging assay. The findings showed that halogenated flavones showed more enzyme inhibitions and antioxidant activities than simple flavones and are potential candidates for the treatment of wide range of diseases.

Synthesis and Pharmacological Properties of 1,3-Bis[(S)Phenylethyl]Imidazolidine-2-Thione

Enantiomerically and diastereomerically pure thiourea derivative (compound I) has been synthesized in two steps starting from (S)-1-phenylethanamine and 1,2-dibromoethane. Compound I was screened for various biochemical parameters including blood glucose level, serum total cholesterol level, serum bilirubin and triglyceride levels, serum glutamate pyruvate transaminase (SGPT) and alkaline phosphatase (ALP) activity in New Zealand White (NZW) rabbits. Compound I was also screened for brine shrimp cytotoxicity, antileishmanial and antioxidant activity. Acute toxicity tests in NZW rabbits were performed and the results showed that compound I was safe up to 2 mg/mL/kg rabbit body weight. For the blood parameters, it was found that compound I caused slightly reduced blood glucose level, increased blood serum bilirubin, ALP and SGPT levels, and caused no changes in cholesterol and triglyceride levels. Thus, results show that compound I possesses good cytotoxic, poor antileishmanial activity, and no prominent antioxidant activity.