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Shah F.A.,Quaid-i-Azam University | Fatima K.,IQ Institute of Infection and Immunity | Sabir S.,Allama Iqbal Open University | Ali S.,Quaid-i-Azam University | And 2 more authors.
Medicinal Chemistry Research | Year: 2015

The discovery and optimization of a novel triorganotin(IV) complexes with anti-HCV properties are presented. Organotin(IV) moiety has the ability to bind phosphate group of RNA backbone. The organotin(IV) moiety is bonded with ligands and groups, which are known for inhibiting HCV enzymes. Triorganotin(IV) complexes were synthesized and evaluated for their potency against HCV by using luciferase assay. Structure-activity relationship studies led to the identification of Tributyltannic[3-(3′4′dichlorophenylamido)propanoate] (compound 1) as a potent HCV inhibitor, with log IC50 values 0.79 nM in the cell-based assay. Triorganotin(IV) complexes containing chlorine and nitro group display higher potency. Gaussia luciferase Assay shows that among triorganotin(IV) derivatives, butyl substituted triorganotin(IV) complexes are more active than methyl- and phenyl-substituted complexes. Graphical abstract: HCV infection can lead to hepatocellular carcinoma, and is a major reason for liver transplantation. The worldwide prevalence of chronic HCV infection is estimated to be approaching 270-300 million people, but patients and physicians are still waiting for effective anti-HCV drugs. With this background, organotin(IV) complexes are synthesized and screened against HCV using Gaussia luciferase assay. Organotin(IV) complexes are selected due to their ability to interact with both DNA constituents and enzymes. [Figure not available: see fulltext.] © 2014 Springer Science+Business Media New York.

Shah M.A.A.,Nanjing Southeast University | Shah M.A.A.,Pmas Arid Agriculture University | Ali Z.,Nanjing Southeast University | Ahmad R.,Nanjing Southeast University | And 3 more authors.
Journal of Nanoscience and Nanotechnology | Year: 2015

Vaccination has led to the eradication of those diseases which had once claimed millions of lives worldwide; however, it is accompanied with a number of dis-advantages especially safety issues until the entry of DNA vaccines. The DNA vaccines have been emerged as the best remedy for problematic diseases being capable of producing humoral and cellular immune responses as well as the safest vaccines so far. However, the magnitude of immune responses produced in primates is lower than that in experimental animals. There are several reasons described theoretically for this limited efficacy and a number of novel approaches have been applied to boost their immune responses, e.g., use of more efficient promoters and coding optimization, addition of traditional or genetic adjuvants, electroporation, intradermal delivery and various prime-boost strategies. One of these strategies is controlled antigen administration of plasmid DNA through microspheres and nanoparticles. This approach is accompanied with a number of advantages to overcome the limitations of traditional delivery systems in terms of stability, solubility and pharmacology. Furthermore, the surface structure of a virus highly resembles with a nanoparticle because of their geometrical regularities and nanoscale dimensions; therefore, the engineering of nanoparticles is based upon principles of natural virus attack which will be the best tool for vaccination. There is evidence that these immune responses can be augmented by properly structured nanosized particles (nanoparticles) that may avoid DNA degradation and facilitate targeted delivery to antigen presenting cells. Adsorption, formulation or encapsulation with particles has been found to stabilize DNA formulations. The use of nanoparticles for DNA vaccine delivery is a platform technology and has been applied for delivery of a variety of existing and potential vaccines successfully. Copyright © 2015 American Scientific Publishers. All rights reserved.

Shah F.A.,Quaid-i-Azam University | Fatima K.,IQ Institute of Infection and Immunity | Sabir S.,Allama Iqbal Open University | Ali S.,Quaid-i-Azam University | Qadri I.,King Abdulaziz University
Applied Organometallic Chemistry | Year: 2014

Gaussia luciferase assay was used to measure the anti-hepatitis C (anti-HCV) potency of tributyltin(IV)[3-(3′,5′-dimethylphenylamido) propanoate] in infected Huh 7.5 cells (human hepatocellular cell). Interaction of the organotin(IV) complex with cetyl N,N,N-trimethylammonium bromide (CTAB) micelles was studied using UV-visible and steady-state florescence spectroscopy. The anti-HCV study showed a log IC50 value of 0.96 nm for the complex. The complex-CTAB interaction parameter showed that partition of the complex from bulk water to the CTAB micelle was a spontaneous process, and the red shift in visible spectra of the complex confirmed its increased solubility into micelles. © 2013 John Wiley & Sons, Ltd.

Shah F.A.,Quaid-i-Azam University | Fatima K.,IQ Institute of Infection and Immunity | Ali S.,Quaid-i-Azam University | Qadri I.,King Abdulaziz University
Infectious Disorders - Drug Targets | Year: 2015

Tributylstannic[3-(3,5 -dimethylphenylamido)propionate]is synthesized and characterized by elemental analysis, FT-IR, multinuclear NMR (1H,13C and119Sn) and mass spectrometry. The organic anion was found to act as monodentate O-bound ligand in solution. The compound was screened for the anti-HCV potency by the Gaussia luciferase Assay using infected Huh 7.5 cells (human hepatocellular cell) and is found active against HCV with logIC50 1.2nM in the cell-based assay. Cationic surfactant cetyl N,N,N-trimethylammoniumbromide (CTAB) was used to study the interactions of the organotin(IV) complex with positively charged micelles of the surfactant acting as a model cell membrane. The thermodynamics parameters of complex- CTAB interaction concluded that the complex is located in the palisade layer of CTAB micelles. The increase in absorbance of visible spectra of the compound confirmed its solubilization into micelles. The two carbonyl oxygen’s were found to be binding sites of the complex with CTAB. © 2015 Bentham Science Publishers.

Fatima K.,IQ Institute of Infection and Immunity | Qadri I.,King Abdulaziz University
Journal of Infection in Developing Countries | Year: 2013

On 22 Feb 2013, the Polio Monitoring Cell of Pakistan announced that the 2012-2013 polio campaign ended, and that 1.6 million children could not be vaccinated due to security concerns in several regions where polio workers had been killed. Those who could not be vaccinated included 50,000 children from the Federally Administrated Tribal Area (FATA), 150,000 form Khyber Pakhtoon Khao, 400,000 from a Quetta, 400,000 from Karachi, and a small number from the Rawalpindi District. These statistics are worrying, as several districts in the large metropolitan cities of Karachi and Quetta were also excluded. The fear of advanced medicine, ideas, or complex devices is a new phenomenon in many conservative and poor countries such as Pakistan, Afghanistan, Sudan, and Somalia. To safeguard the safety of the rest of the world, the failure in the implementation of WHO guidelines for vaccination must be regulated by the UN. There are a number of reasons for the phobias surrounding vaccination, but as technology continues to evolve at such a rapid rate, those with self-determined ideologies cannot cope with such advances. They become vocal to gain popularity and prevent the use of these technologies and medicine by creating and spreading rumors and propaganda of expediency. The struggle to vaccinate children is not easily understood by anyone living in the developed world. The irrational fear of vaccines and the lack of vaccination pose a serious global health risk and must be curbed through a wide variety of pro-vaccination media and religious campaigns. © 2013 Fatima et al.

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