18 results on '"Akram, Muhammad Safwan"'
Search Results
2. Challenges for biosimilars: focus on rheumatoid arthritis.
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Akram, Muhammad Safwan, Pery, Neelam, Butler, Lucy, Shafiq, Muhammad Imtiaz, Batool, Nayab, Rehman, Muhammad Fayyaz ur, Grahame-Dunn, Luke G., and Yetisen, Ali K.
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RHEUMATOID arthritis , *BIOSIMILARS , *MEDICAL personnel , *REGULATORY compliance , *REGENERATIVE medicine , *GENE therapy , *MONOCLONAL antibodies - Abstract
Healthcare systems worldwide are struggling to find ways to fund the cost of innovative treatments such as gene therapies, regenerative medicine, and monoclonal antibodies (mAbs). As the world's best known mAbs are close to facing patent expirations, the biosimilars market is poised to grow with the hope of bringing prices down for cancer treatment and autoimmune disorders, however, this has yet to be realized. The development costs of biosimilars are significantly higher than their generic equivalents due to therapeutic equivalence trials and higher manufacturing costs. It is imperative that academics and relevant companies understand the costs and stages associated with biologics processing. This article brings these costs to the forefront with a focus on biosimilars being developed for Rheumatoid Arthritis (RA). mAbs have remarkably changed the treatment landscape, establishing their superior efficacy over traditional small chemicals. Five blockbuster TNFα mAbs, considered as first line biologics against RA, are either at the end of their patent life or have already expired and manufacturers are seeking to capture a significant portion of that market. Although in principle, market-share should be available, withstanding that the challenges regarding the compliance and regulations are being resolved, particularly with regards to variation in the glycosylation patterns and challenges associated with manufacturing. Glycan variants can significantly affect the quality attributes requiring characterization throughout production. Successful penetration of biologics can drive down prices and this will be a welcome change for patients and the healthcare providers. Herein we review the biologic TNFα inhibitors, which are on the market, in development, and the challenges being faced by biosimilar manufacturers. [ABSTRACT FROM AUTHOR]
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- 2021
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3. Wasting cash—the decline of the British biotech sector.
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Smith, Graham, Akram, Muhammad Safwan, Redpath, Keith, and Bains, William
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BIOTECHNOLOGY industries , *CORPORATE finance , *CORPORATE directors' salaries , *LABOR incentives , *RESOURCE allocation - Abstract
The article assesses the decline of the biotechnology industry in Great Britain. The authors assert that this decline can be attributed to a combination of severe undercapitalization of British companies, overgenerous remuneration to board members and absence of share- or performance-related reward for top executives. Compared to its American counterpart, the British biotechnology industry has no world-class companies in the mold of Amgen, Genentech or Genzyme. British companies also failed to invest their limited resources in product development and innovative therapeutics.
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- 2009
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4. Synthesis, Crystal Structure, DFT Calculations, Hirshfeld Surface Analysis and In Silico Drug-Target Profiling of (R)-2-(2-(1,3-Dioxoisoindolin-2-yl)propanamido)benzoic Acid Methyl Ester.
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Rubab, Syeda Laila, Raza, Abdul Rauf, Nisar, Bushra, Ashfaq, Muhammad, Altaf, Yasir, Hussain, Riaz, Sajjad, Noreen, Akram, Muhammad Safwan, Tahir, Muhammad Nawaz, Shaheen, Muhammad Ashraf, Rehman, Muhammad Fayyaz ur, and Ali, Hayssam M.
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SURFACE analysis , *CRYSTAL structure , *PHTHALIC anhydride , *CHEMICAL properties , *DNA topoisomerase II , *METHYL formate , *BENZOIC acid - Abstract
The work here reflects synthesis, DFT studies, Hirshfeld charge analysis and crystal data exploration of pharmacologically important (R)-2-(2-(1,3-dioxoisoindolin-2-yl)propanamido)benzoic acid methyl ester (5) to understand its properties for further chemical transformations. The methyl anthranilate (2) was produced by the esterification of anthranilic acid in an acidic medium. The phthaloyl-protected alanine (4) was rendered by the fusion of alanine with phthalic anhydride at 150 °C, followed by coupling with (2) furnished isoindole (5). The characterization of products was performed using IR, UV-Vis, NMR and MS. Single-crystal XRD also verified the structure of (5) in which N-H⋯O bonding stabilizes the molecular configuration of (5), resulting in the formation of S(6) hydrogen-bonded loop. The molecules of isoindole (5) are connected in the form of dimers, and the π⋯π stacking interaction between aromatic rings further stabilizes the crystal packing. DFT studies suggest that HOMO is over the substituted aromatic ring, the LUMO is present mainly over the indole side, and nucleophilic and electrophilic corners point out the reactivity of the product (5). In vitro and in silico analysis of (5) shows its potential as an antibacterial agent targeting DNA gyrase and Dihydroorotase from E. coli and tyrosyl-tRNA synthetase and DNA gyrase from Staphylococcus aureus. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Antimicrobial metal-based thiophene derived compounds.
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Yasmeen, Shakeela, Sumrra, Sajjad Hussain, Akram, Muhammad Safwan, and Chohan, Zahid H.
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THIOPHENE derivatives , *COPPER compounds , *NICKEL compounds , *ZINC compounds , *ESCHERICHIA coli - Abstract
A novel series of thiophene derived Schiff bases and their transition metal- [Co(II), Cu(II), Zn(II), Ni(II)] based compounds are reported. The Schiff bases act as tridentate ligands toward metal ions via azomethine-N, deprotonated-N of ammine substituents and S-atom of thienyl moiety. The synthesized ligands along with their metal complexes were screened for theirin vitroantibacterial activity against six bacterial pathogens(Escherichia coli,Shigella flexneri,Pseudomonas aeruginosa,Salmonella typhi,Staphylococcus aureusandBacillus subtilis) and for antifungal activity against six fungal pathogens (Trichophytonlongifusus,Candida albicans,Aspergillus flavus,Microsporum canis,Fusarium solaniandCandida glabrata). The results of antimicrobial studies revealed the free ligands to possess potential activity which significantly increased upon chelation. [ABSTRACT FROM AUTHOR]
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- 2017
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6. Metal-based ethanolamine-derived compounds: a note on their synthesis, characterization and bioactivity.
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Amjad, Muhammad, Sumrra, Sajjad H., Akram, Muhammad Safwan, and Chohan, Zahid H.
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ETHANOLAMINES , *ANTIBACTERIAL agents , *ANTIFUNGAL agents , *PSEUDOMONAS aeruginosa , *SALMONELLA typhi - Abstract
Metal-based ethanolamines,(L1)–(L4)coordinated with Co(II), Cu(II), Ni(II) and Zn(II) metals in 1:2 (metal:ligand) molar ratio to produce new compounds have been reported. These compounds were screened for their bactericidal/fungicidal activity against a number of bacterial (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureusandBacillus subtilis) and fungal strains (Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solaniandCandida glabrata) alongside against a shrimp species known asArtemia salina. The screening results indicated that metal complexes have significantly higher activity than uncomplexed ligands against one or more bacterial/fungal species due to chelation. The ligand (L4) displayed good bacterial and fungal activity as compared to other ligands. The antibacterial results revealed that the Zn(II) complex(16)of (L4) was found to be the most active complex and Co(II) complex(14)of the same ligand (L4), demonstrated the highest antifungal activity. [ABSTRACT FROM PUBLISHER]
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- 2016
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7. Effect of different end-capped donor moieties on non-fullerenes based non-covalently fused-ring derivatives for achieving high-performance NLO properties.
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Khalid, Muhammad, Shafiq, Iqra, Umm-e-Hani, Mahmood, Khalid, Hussain, Riaz, ur Rehman, Muhammad Fayyaz, Assiri, Mohammed A., Imran, Muhammad, and Akram, Muhammad Safwan
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FULLERENE derivatives , *FULLERENES , *FRONTIER orbitals , *DENSITY matrices , *NATURAL orbitals , *BAND gaps , *DENSITY of states - Abstract
A series of derivatives (DOCD2–DOCD6) with D–π–A configuration was designed by substituting various efficient donor moieties via the structural tailoring of o-DOC6-2F. Quantum-chemical approaches were used to analyze the optoelectronic properties of the designed chromophores. Particularly, M06/6-311G(d,p) functional was employed to investigate the non-linear optical (NLO) response (linear polarizability ⟨α⟩, first (βtot) and second (γ tot) order hyperpolarizabilities) of the designed derivatives. A variety of analyses such as frontier molecular orbital (FMO), absorption spectra, transition density matrix (TDMs), density of states (DOS), natural bond orbital (NBO) and global reactivity parameters (GRPs) were employed to explore the optoelectronic response of aforementioned chromophores. FMO investigation revealed that DOCD2 showed the least energy gap (1.657 eV) among all the compounds with an excellent transference of charge towards the acceptor from the donor. Further, DOS pictographs and TDMs heat maps also supported FMO results, corroborating the presence of charge separation states along with efficient charge transitions. NBO analysis showed that π-linker and donors possessed positive charges while acceptors retained negative charges confirming the D–π–A architecture of the studied compounds. The λmax values of designed chromophores (659.070–717.875 nm) were found to have broader spectra. The GRPs were also examined utilizing energy band gaps of EHOMO and ELUMO for the entitled compounds. Among all the derivatives, DOCD2 showed the highest values of βtot (7.184 × 10–27 esu) and γ tot (1.676 × 10–31 esu), in coherence with the reduced band gap (1.657 eV), indicating future potentiality for NLO materials. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Evaluating Zn‐Porphyrin‐Based Near‐IR‐Sensitive Non‐Fullerene Acceptors for Efficient Panchromatic Organic Solar Cells.
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Khan, Muhammad Usman, Imran., Muhammad, Rehman, Muhammad Fayyaz ur, Assiri, Mohammed A., Mashhadi, Syed Muddassir Ali, Akram, Muhammad Safwan, and Lu, Changrui
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SOLAR cells , *ELECTRON mobility , *HOLE mobility , *BAND gaps , *BINDING energy , *OPEN-circuit voltage , *PHOTOVOLTAIC power systems - Abstract
Porphyrin‐based non‐fullerene acceptors (NFAs) have shown pronounced potential for assembling low‐bandgap materials with near‐infrared (NIR) characteristics. Herein, panchromatic‐type porphyrin‐based molecules (POR1–POR5) are proposed by modulating end‐capped acceptors of a highly efficient porphyrin‐based NFA PORTFIC(POR) for organic solar cells (OSCs). Quantum chemical structure‐property relationship has been studied to discover photovoltaic and optoelectronic characteristics of POR1–POR5. Results show that optoelectronic properties of the POR1–POR5 are better in all aspects when compared with the reference POR. All proposed NFAs particularly POR5 proved to be the preferable porphyrin‐based NIR sensitive NFA for OSCs applications owing to lower energy gap (1.56 eV), transition energy (1.11 eV), binding energy (Eb=0.986 eV), electron mobility (λe=0.007013Eh), hole mobility (λh=0.004686 Eh), high λmax=1116.27 nm and open‐circuit voltage (Voc=1.96 V) values in contrast to the reference POR and other proposed NFAs. This quantum chemical insight provides sufficient evidence about excellent potential of the proposed porphyrin‐based NIR sensitive NFA derivatives for their use in OSCs. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Exploration of promising optical and electronic properties of (non-polymer) small donor molecules for organic solar cells.
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Khalid, Muhammad, Khan, Muhammad Usman, Ahmed, Saeed, Shafiq, Zahid, Alam, Mohammed Mujahid, Imran, Muhammad, Braga, Ataualpa Albert Carmo, and Akram, Muhammad Safwan
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PHOTOVOLTAIC power systems , *SOLAR cells , *SMALL molecules , *FRONTIER orbitals , *OPEN-circuit voltage , *OPTICAL properties , *ALKOXY compounds - Abstract
Non-fullerene based organic compounds are considered promising materials for the fabrication of modern photovoltaic materials. Non-fullerene-based organic solar cells comprise of good photochemical and thermal stability along with longer device lifetimes as compared to fullerene-based compounds. Five new non-fullerene donor molecules were designed keeping in view the excellent donor properties of 3-bis(4-(2-ethylhexyl)-thiophen-2-yl)-5,7-bis(2ethylhexyl) benzo[1,2-:4,5-c′]-dithiophene-4,8-dione thiophene-alkoxy benzene-thiophene indenedione (BDD-IN) by end-capped modifications. Photovoltaic and electronic characteristics of studied molecules were determined by employing density functional theory (DFT) and time dependent density functional theory (TD-DFT). Subsequently, obtained results were compared with the reference molecule BDD-IN. The designed molecules presented lower energy difference (ΔΕ) in the range of 2.17–2.39 eV in comparison to BDD-IN (= 2.72 eV). Moreover, insight from the frontier molecular orbital (FMO) analysis disclosed that central acceptors are responsible for the charge transformation. The designed molecules were found with higher λmax values and lower transition energies than BDD-IN molecule due to stronger end-capped acceptors. Open circuit voltage (Voc) was observed in the higher range (1.54–1.78 V) in accordance with HOMOdonor–LUMOPC61BM by designed compounds when compared with BDD-IN (1.28 V). Similarly, lower reorganization energy values were exhibited by the designed compounds in the range of λe(0.00285–0.00370 Eh) and λh(0.00847–0.00802 Eh) than BDD-IN [λe(0.00700 Eh) and λh(0.00889 Eh)]. These measurements show that the designed compounds are promising candidates for incorporation into solar cell devices, which would benefit from better hole and electron mobility. [ABSTRACT FROM AUTHOR]
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- 2021
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10. Molecular engineering of indenoindene-3-ethylrodanine acceptors with A2-A1-D-A1-A2 architecture for promising fullerene-free organic solar cells.
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Khalid, Muhammad, Momina, Imran, Muhammad, Rehman, Muhammad Fayyaz ur, Braga, Ataualpa Albert Carmo, and Akram, Muhammad Safwan
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SOLAR cells , *FRONTIER orbitals , *CHARGE transfer , *DENSITY matrices , *DENSITY functional theory , *OPEN-circuit voltage , *POLYMER blends , *POLYMERS - Abstract
Considering the increased demand and potential of photovoltaic devices in clean, renewable electrical and hi-tech applications, non-fullerene acceptor (NFA) chromophores have gained significant attention. Herein, six novel NFA molecules IBRD1–IBRD6 have been designed by structural modification of the terminal moieties from experimentally synthesized A2-A1-D-A1-A2 architecture IBR for better integration in organic solar cells (OSCs). To exploit the electronic, photophysical and photovoltaic behavior, density functional theory/time dependent-density functional theory (DFT/TD-DFT) computations were performed at M06/6-311G(d,p) functional. The geometry, electrical and optical properties of the designed acceptor molecules were compared with reported IBR architecture. Interestingly, a reduction in bandgap (2.528–2.126 eV), with a broader absorption spectrum, was studied in IBR derivatives (2.734 eV). Additionally, frontier molecular orbital findings revealed an excellent transfer of charge from donor to terminal acceptors and the central indenoindene-core was considered responsible for the charge transfer. Among all the chromophores, IBRD3 manifested the lowest energy gap (2.126 eV) with higher λmax at 734 and 745 nm in gaseous phase and solvent (chloroform), respectively due to the strong electron-withdrawing effect of five end-capped cyano groups present on the terminal acceptor. The transition density matrix map revealed an excellent charge transfer from donor to terminal acceptors. Further, to investigate the charge transfer and open-circuit voltage (Voc), PBDBT donor polymer was blended with acceptor chromophores, and a significant Voc (0.696–1.854 V) was observed. Intriguingly, all compounds exhibited lower reorganization and binding energy with a higher exciton dissociation in an excited state. This investigation indicates that these designed chromophores can serve as excellent electron acceptor molecules in organic solar cells (OSCs) that make them attractive candidates for the development of scalable and inexpensive optoelectronic devices. [ABSTRACT FROM AUTHOR]
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- 2021
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11. Exploration of efficient electron acceptors for organic solar cells: rational design of indacenodithiophene based non-fullerene compounds.
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Khalid, Muhammad, Khan, Muhammad Usman, -Razia, Eisha-tul, Shafiq, Zahid, Alam, Mohammed Mujahid, Imran, Muhammad, and Akram, Muhammad Safwan
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SOLAR cells , *ELECTROPHILES , *OPEN-circuit voltage , *FRONTIER orbitals , *RENEWABLE energy sources , *FULLERENES , *REORGANIZATION energy - Abstract
The global need for renewable sources of energy has compelled researchers to explore new sources and improve the efficiency of the existing technologies. Solar energy is considered to be one of the best options to resolve climate and energy crises because of its long-term stability and pollution free energy production. Herein, we have synthesized a small acceptor compound (TPDR) and have utilized for rational designing of non-fullerene chromophores (TPD1–TPD6) using end-capped manipulation in A2–A1–D–A1–A2 configuration. The quantum chemical study (DFT/TD-DFT) was used to characterize the effect of end group redistribution through frontier molecular orbital (FMO), optical absorption, reorganization energy, open circuit voltage (Voc), photovoltaic properties and intermolecular charge transfer for the designed compounds. FMO data exhibited that TPD5 had the least ΔE (1.71 eV) with highest maximum absorption (λmax) among all compounds due to the four cyano groups as the end-capped acceptor moieties. The reorganization energies of TPD1–TPD6 hinted at credible electron transportation due to the lower values of λe than λh. Furthermore, open circuit voltage (Voc) values showed similar amplitude for all compounds including parent chromophore, except TPD4 and TPD5 compounds. These designed compounds with unique end group acceptors have the potential to be used as novel fabrication materials for energy devices. [ABSTRACT FROM AUTHOR]
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- 2021
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12. Consanguineous marriages increase the incidence of recurrent tuberculosis: Evidence from whole exome sequencing.
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Akbar, Noor ul, Ahmad, Sajjad, Khan, Taj Ali, Tayyeb, Muhammad, Akhter, Naheed, Shafiq, Laraib, Khan, Shahid Niaz, Alam, Mohammad Mahtab, Abdullah, Alduwish Manal, Rehman, Muhammad Fayyaz ur, Bajaber, Majed A., and Akram, Muhammad Safwan
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CONSANGUINITY , *MYCOBACTERIAL diseases , *TUBERCULOSIS , *PRIMARY immunodeficiency diseases , *BCG vaccines , *TUBERCULOSIS in cattle - Abstract
In this study, we have identified multiple mutations in the IL-12R1 gene among Pakistani patients who have inherited them through consanguineous marriages. These patients have experienced severe Bacille-Calmette-Guérin (BCG) infection as well as recurrent tuberculosis. We will demonstrate the pivotal role of interleukin (IL)-12/interferon (IFN)-γ axis in the regulation of mycobacterial diseases. First, we checked the patients' medical records, and then afterward, we assessed interferon-gamma (IFN-γ) production through ELISA. Following that, DNA was extracted to investigate IL-12/IFN- abnormalities. Whole exome sequencing was conducted through Sanger sequencing. Secretory cytokine levels were compared from healthy control of the same age groups and they were found to be considerably less in the disease cohort. To evaluate the probable functional impact of these alterations, an in silico study was performed. The study found that the patients' PBMCs produced considerably less IFN-γ than expected. Analysis using flow cytometry showed that activated T cells lacked surface expression of IL-12Rβ1. Exon 7 of the IL-12Rβ1 gene, which encodes a portion of the cytokine binding region (CBR), and exon 10, which encodes the fibronectin-type III (FNIII) domain, were found to have the mutations c.641 A > G; p.Q214R and c.1094 T > C; p.M365T, respectively. In silico analysis showed that these mutations likely to have a deleterious effect on protein function. Our findings indicate the significant contribution of the IL-12/IFN-γ is in combating infections due to mycobacterium. Among Pakistani patients born to consanguineous marriages, the identified mutations in the IL-12Rβ-1 gene provide insights into the genetic basis of severe BCG infections and recurrent tuberculosis. The study highlights the potential utility of newborn screening in regions with mandatory BCG vaccination, enabling early detection and intervention for primary immunodeficiencies associated with mycobacterial infections. Moreover, the study suggests at the potential role of other related genes such as IL-23Rβ1, TYK2, or JAK2 in IFN-γ production, warranting further investigation. • Deleterious mutations in the IL-2Rβ-1gene among patients born to consanguineous marriages. • The study highlights the pivotal role of the interleukin (IL)-12/interferon (IFN)-γ axis in regulating mycobacterial diseases. • Secretory cytokine levels are compared with healthy controls of the same age group, revealing significant differences in the disease cohort. • Flow cytometry analysis reveals that activated T cells lack surface expression of IL-12Rβ1. • The study demonstrates application of these mutations to be screened in newborns. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Exploration of photovoltaic behavior of fused triphenylamine moiety as core donor with modified acceptors: Star-shaped D-[formula omitted]-A conjugated systems.
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Khalid, Muhammad, Habiba Ishaque, Ume, Asghar, Muhammad Adnan, Adeel, Muhammad, Alam, Mohammed Mujahid, Imran, Muhammad, Baby, Rabia, Braga, Ataualpa A.C., Fayyaz ur Rehman, Muhammad, and Akram, Muhammad Safwan
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TRIPHENYLAMINE , *OPEN-circuit voltage , *SOLAR cells , *BINDING energy , *MOIETIES (Chemistry) , *BAND gaps - Abstract
Fullerene-free organic chromophores have drawn considerable attention as successful photonic devices for organic solar cells. So, a series of novel non-fullerene-based donor molecules (HBTD2–HBTD9) were fabricated via structural modification of the terminal acceptor groups from HBTR1. In order to achieve the photovoltaic, photophysical, and electronic behavior of fore-said compounds, density functional theory/time-dependent density functional theory (DFT/TD-DFT) based analyses were accomplished at B3LYP functional along with 6-311G(d,p) basis set. The optical and electrical characteristics of the derivatives were compared with HBTR1 architecture. All designed molecules exhibited a lower E HOMO - E LUMO band gap (2.183–4.106 eV) with a red shift in absorbance compared to the reference compound (4.179 eV). All derivatives (HBTD2–HBTD9), except HBTD3 , showed a greater exciton dissociation rate due to low binding energy (E b = −0.337 to 1.400 eV) when compared with HBTR1 (E b = 1.401 eV). Interestingly, HBTD9 manifested to be the prime candidate for non-fullerene organic solar cells (NF–OSCs) owing to the lowest energy band gap, large mobility of charges, and least value of binding energy while holding an excellent redshift value compared to all the designed chromophores. This study revealed that these chromophores would be potential competitors in manufacturing effective optoelectronic materials. • Designing of acridine based donor materials (HBTD2 - HBTD9) from HBTR1 via efficient acceptors. • Study of photovoltaic properties of aforesaid compounds through DFT. • Investigation of opto-electronic properties at B3LYP/6-311G(d,p) functional of DFT. • Efficacy of designed compounds was explored by investigating open circuit voltage. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Synthesis, crystal structure determination, biological screening and docking studies of N1-substituted derivatives of 2,3-dihydroquinazolin-4(1H)-one as inhibitors of cholinesterases.
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Sultana, Nargis, Sarfraz, Muhammad, Tanoli, Saba Tahir, Akram, Muhammad Safwan, Sadiq, Abdul, Rashid, Umer, and Tariq, Muhammad Ilyas
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CRYSTAL structure , *CHOLINESTERASES , *PHARMACOKINETICS , *CARCINOGENICITY , *CHEMICAL inhibitors - Abstract
Pursuing the strategy of developing potent AChE inhibitors, we attempted to carry out the N 1 -substitution of 2,3-dihydroquinazolin-4(1 H )-one core. A set of 32 N-alkylated/benzylated quinazoline derivatives were synthesized, characterized and evaluated for their inhibition against cholinesterases. N-alkylation of the series of the compounds reported previously (N-unsubstituted) resulted in improved activity. All the compounds showed inhibition of both enzymes in the micromolar to submicromolar range. Structure activity relationship (SAR) of the 32 derivatives showed that N-benzylated compounds possess good activity than N-alkylated compounds. N-benzylated compounds 2ad and 2af were found very active with their IC 50 values toward AChE in submicromolar range (0.8 µM and 0.6 µM respectively). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. Computational predictions of ADMET studies reveal that all the compounds have good pharmacokinetic properties with no AMES toxicity and carcinogenicity. Moreover, all the compounds are predicted to be absorbed in human intestine and also have the ability to cross blood brain barrier. Overall, the synthesized compounds have established a structural foundation for the design of new inhibitors of cholinesterase. [ABSTRACT FROM AUTHOR]
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- 2017
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15. Synthesis, biological evaluation and docking studies of 2,3-dihydroquinazolin-4(1H)-one derivatives as inhibitors of cholinesterases.
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Sarfraz, Muhammad, Sultana, Nargis, Tariq, Muhammad Ilyas, Rashid, Umer, Akram, Muhammad Safwan, and Sadiq, Abdul
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QUINAZOLINE , *MOLECULAR docking , *CHOLINESTERASES , *GALANTHAMINE , *DONEPEZIL - Abstract
In search of potent inhibitors of cholinesterases, we have synthesized and evaluate a number of 2,3-dihydroquinazolin-4(1H)-one derivatives. The synthetic approach provided an efficient synthesis of the target molecules with excellent yield. All the tested compounds showed activity against both the enzymes in micromolar range. In many case, the inhibition of both enzymes are higher than or comparable to the standard drug galatamine. With the selectivity index of 2.3 for AChE, compound 5f can be considered as a potential lead compound with a feature of dual AChE/BChE inhibition with IC 50 = 1.6 ± 0.10 μM (AChE) and 3.7 ± 0.18 μM (BChE). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. The computed binding modes of these compounds in the active site of AChE and BChE provide an insight into the mechanism of inhibition of these two enzyme. [ABSTRACT FROM AUTHOR]
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- 2017
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16. Metal based drugs: design, synthesis and in-vitro antimicrobial screening of Co(II), Ni(II), Cu(II) and Zn(II) complexes with some new carboxamide derived compounds: crystal structures of N-[ethyl(propan-2-yl)carbamothioyl]thiophene-2-carboxamide and its copper(II) complex
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Sumrra, Sajjad H., Hanif, Muhammad, Chohan, Zahid H., Akram, Muhammad Safwan, Akhtar, Javeed, and Al-Shehri, Saad M.
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IN vitro studies , *ANTI-infective agents , *THIOPHENE derivatives , *CARBOXAMIDES , *MASS spectrometry , *LIGANDS (Biochemistry) - Abstract
A new series of compounds derived from thiophene-2-carboxamide were synthesized and characterized by IR,1H-NMR and13C-NMR, mass spectrometry and elemental analysis. These compounds were further used to prepare their Co(II), Ni(II), Cu(II) and Zn(II) metal complexes. All metal(II) complexes were air and moisture stable. Physical, spectral and analytical data have shown the Ni(II) and Cu(II) complexes to exhibit distorted square-planar and Co(II) and Zn(II) complexes tetrahedral geometries. The ligand (L1) and its Cu(II) complex were characterized by the single-crystal X-ray diffraction method. All the ligands and their metal(II) complexes were screened for theirin-vitroantimicrobial activity. The antibacterial and antifungal bioactivity data showed that the metal(II) complexes were found to be more potent than the parent ligands against one or more bacterial and fungal strains. [ABSTRACT FROM AUTHOR]
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- 2016
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17. The regulation of mobile medical applications.
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Yetisen, Ali Kemal, Martinez-Hurtado, J. L., da Cruz Vasconcellos, Fernando, Simsekler, M. C. Emre, Akram, Muhammad Safwan, and Lowe, Christopher R.
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MOBILE apps , *MEDICAL software , *DIAGNOSTIC imaging , *LABS on a chip , *MINIATURE electronic equipment , *MICROFLUIDIC analytical techniques , *NANOTECHNOLOGY , *MICROFLUIDICS - Abstract
The rapidly expanding number of mobile medical applications have the potential to transform the patient–healthcare provider relationship by improving the turnaround time and reducing costs. In September 2013, the U.S. Food and Drug Administration (FDA) issued guidance to regulate these applications and protect consumers by minimising the risks associated with their unintended use. This guidance distinguishes between the subset of mobile medical apps which may be subject to regulation and those that are not. The marketing claims of the application determine the intent. Areas of concern include compliance with regular updates of the operating systems and of the mobile medical apps themselves. In this article, we explain the essence of this FDA guidance by providing examples and evaluating the impact on academia, industry and other key stakeholders, such as patients and clinicians. Our assessment indicates that awareness and incorporation of the guidelines into product development can hasten the commercialisation and market entry process. Furthermore, potential obstacles have been discussed and directions for future development suggested. [ABSTRACT FROM AUTHOR]
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- 2014
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18. Tailor-made recombinant prokaryotic lectins for characterisation of glycoproteins.
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Fernandez-Poza, S., Padros, A., Thompson, R., Butler, Lucy, Islam, Meez, Mosely, J.A., Scrivens, James H., F Rehman, Muhammad, and Akram, Muhammad Safwan
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PLANT lectins , *GLYCANS , *LECTINS , *GALACTOSE , *GLYCOPROTEINS , *PROTEIN engineering , *PLANT performance , *SIALIC acids - Abstract
Development of biosimilars is costly, where glycan analysis is a significant constraint on time and money. This paper provides an in-depth characterisation of several novel recombinant prokaryotic lectins (RPLs), developed through directed evolution, displaying specific binding activities to α-mannose, β-galactose, fucose and sialic acid residues, tested against major biosimilar targets. The binding characterisation of all lectins was performed employing the principles of bio-layer interferometry (BLI), with help of the streptavidin-coated sensor with the biotinylated lectins. The binding activity of the RPLs and the specificity to a broad range of glycoproteins and glycoconjugates were evaluated and compared to those of equivalent plant-derived lectins. While exhibiting better or similar specificity, RPLs displayed significantly better binding in all cases. The binding mechanisms are explained with particular focus on the role hydrogen bonding plays in the change of specificity for a galactose specific lectin. Furthermore, different sets of RPLs and their plant equivalents were assayed against the different glycoprotein targets to evaluate the analytical parameters of the lectin-glycoprotein interaction. The obtained LoDs reached by the RPLs were lower than those of their plant counterparts apart from one, exhibiting RPL:PL LoD ratios of 0.8, 2.5, 14.2 and 380 for the sets of lectins specific to fucose, α-mannose, β-galactose and sialic acid, respectively. Such enhancement in analytical parameters of RPLs shows their applicability in protein purification and as bioanalytical tools for glycan analysis and biosensor development. A. Formation of the sensogram curves from the lectin affinity assay performed on an Octet platform. Involving the most relevant assay steps: (1) Immobilisation of the biotinylated lectins (2) sugar binding and (3) quenching.B. Binding curves for the assessed plant lectins (red) and the recombinant counterparts (blue) assayed against proteins displaying different glycan groups in this paper. [Display omitted] • Novel recombinant prokaryotic lectins with enhanced specificity towards respective glycans. • Detailed comparison with plant lectins with affinity towards the same glycoforms. • Example of changing the specificity of one of the lectins through protein engineering. • Testing performance of microbial & plant lectins against a selection of glycoproteins. • Demonstrating improved binding kinetics for recombinant prokaryotic lectins. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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