2-Furoic piperazide derivatives as promising drug candidates of type 2 diabetes and Alzheimer’s diseases: <i>In vitro</i> and <i>in silico</i> studies

Abbasi, Muhammad Athar,Hassan, Mubashir,ur-Rehman, Aziz,Siddiqui, Sabahat Zahra,Hussain, Ghulam,Shah, Syed Adnan Ali,Ashraf, Muhammad,Shahid, Muhammad,Seo, Sung Yum Elsevier 2018 Computational biology and chemistry Vol.77 No.-

<P><B>Abstract</B></P> <P>The heterocyclic compounds have been extensively reported for their bioactivity potential. The current research work reports the synthesis of some new multi-functional derivatives of 2-furoic piperazide (<B>1</B>; 1-(2-furoyl)piperazine). The synthesis was initiated by reacting the starting compound <B>1</B> with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (<B>2</B>) in a basic, polar and protic medium to obtain the parent sulfonamide <B>3</B> which was then treated with different electrophiles, <B>4a–g</B>, in a polar and aprotic medium to acquire the designed molecules, <B>5a</B>–<B>g</B>. These convergent derivatives were evaluated for their inhibitory potential against <I>α</I>-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Acarbose was used as a reference standard for <I>α</I>-glucosidase inhibition while eserine for AChE and BChE inhibition. Some of the synthesized compounds were identified as promising inhibitors of these three enzymes and their bioactivity potentials were also supported by molecular docking study. The most active compounds among the synthetic analogues might be helpful in drug discovery and development for the treatment of type 2 diabetes and Alzhiemer’s diseases.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Synthesis of multi-functional 2-furoic piperazide derivatives. </LI> <LI> Enzyme inhibitory studies against different enzymes. </LI> <LI> Computational studies to augment the <I>in vitro</I> results. </LI> <LI> Suitable therapeutic agents for type 2 diabetes and Alzheimer’s disease. </LI> <LI> Mild hemolytic agents toward red blood cell membrane. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Structure-activity relationship and in silico study of unique bi-heterocycles: 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazole-2-thiol derivatives

Abbasi Athar, Muhammad,Ramzan Shahid, Muhammad,Aziz-Ur-Rehman, A,Siddiqui Zahra, Sabahat,Hassan, Mubashir,Raza, Hussain,Shah Adnan, Syed,Mirza, Bushra,Seo, Sung-Yum National Library of Serbia 2019 Journal of the Serbian Chemical Society Vol.84 No.7

Ground state opto-electronic and thermoelectric response of cubic XSnO3 (X = Ba, Sr) compounds

M. Bilal Saddique,Muhammad Rashid,Adnan Afzal,Shahid M. Ramay,Farooq Aziz,Asif Mahmood 한국물리학회 2017 Current Applied Physics Vol.17 No.8

The density functional has been implemented to deliberate the cubic perovskite XSnO3 (X ¼ Ba, Sr) for their elastic, electronic, optical as well as thermoelectric characteristic. The XSnO3 (X ¼ Ba, Sr) illustrates good pact of lattice parameter for these iso-structural compounds having cubic perovskite structure. The generalized gradient approximation based on the exchange-correlation functional is applied for computing structural and mechanical characteristic, whereas the electronic, optical and thermoelectric properties have been studied by the functional suggested by Tran and Blaha that is termed as of modified Becke-Johnson (mBJ) functional. The thermodynamics stability is recognized through the expression of enthalpies of formation, which is further verified from the calculated structural properties of cubic perovskite XSnO3 (X ¼ Ba, Sr). Moreover, various elastic parameters such has bulk modules B, Cij, shear modulus G, Young's modulus Y, anisotropy factor, B/G ratio and Poisson's ratio n have also been reported. It has been observed by band structure computation that the studied compounds exhibit an indirect band gap between the unoccupied Ba/Sr 6s/5s and the occupied O 2p orbitals. Detailed study of optical properties is presented under the incident photon energy upto 28 eV. Our computed static dielectric constant ε2(0) and refractive index n(0) are comparable with other theoretical and experimental values. Thermoelectric properties are presented in terms of computed Seebeck coefficient, electrical and thermal conductivities and their variation with the rise in temperature suggest that the studied compounds may find applications in the construction of various thermo-electric devices.

Exploration of synthetic multifunctional amides as new therapeutic agents for Alzheimer's disease through enzyme inhibition, chemoinformatic properties, molecular docking and dynamic simulation insights

Hassan, Mubashir,Abbasi, Muhammad Athar,Aziz-ur-Rehman, Muhammad Athar,Siddiqui, Sabahat Zahra,Hussain, Ghulam,Shah, Syed Adnan Ali,Shahid, Muhammad,Seo, Sung-Yum Elsevier 2018 Journal of theoretical biology Vol.458 No.-

<P><B>Abstract</B></P> <P>A new series of multifunctional amides has been synthesized having moderate enzyme inhibitory potentials and mild cytotoxicity. 2-Furyl(1-piperazinyl)methanone (<B>1</B>) was coupled with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (<B>2</B>) to form {4-[(3,5-dichloro-2-hydroxyphenyl)sulfonyl]-1-piperazinyl}(2-furyl)methanone (<B>3</B>). Different elecrophiles were synthesized by the reaction of various un/substituted anilines (<B>4a-o</B>) with 2-bromoacetylbromide (<B>5</B>), 2‑bromo‑<I>N</I>-(un/substituted-phenyl)acetamides (<B>6a-o</B>). Further, equimolar ratios of <B>3</B> and <B>6a-o</B> were allowed to react in the presence of K<SUB>2</SUB>CO<SUB>3</SUB> in acetonitrile to form desired multifunctional amides (<B>7a-o</B>). The structural confirmation of all the synthesized compounds was carried out by their EI-MS, IR, <SUP>1</SUP>H NMR and <SUP>13</SUP>C NMR spectral data. Enzyme inhibition activity was performed against acetyl and butyrylcholinestrase enzymes, whereby <B>7e</B> showed very good activity having IC<SUB>50</SUB> value of 5.54 ± 0.03 and 9.15 ± 0.01 <I>μ</I>M, respectively, relative to eserine, a reference standard. Hemolytic activity of the molecules was checked to asertain their cytotoxicity towards red blood cell membrance and it was observed that most of the compounds were not toxic up to certain range. Moreover, chemoinformatic protepties and docking simulation results also showed the significance of <B>7e</B> as compared to other compounds. Based on <I>in vitro</I> and <I>in silico</I> analysis <B>7e</B> could be used as a template for the development of new drugs against Alzheimer's disease.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Designing of multifunctional amides derivatives as acetyl and butyrylcholinesterase inhibitors. </LI> <LI> Chemoinformatic, molecular docking and simulation analysis was against most potent inhibitor <B>7e.</B> </LI> <LI> In vitro and in silico results showed the significance of <B>7e</B> and could be used as a template for novel drugs against Alzheimer's disease. </LI> </UL> </P>

Designing of promising medicinal scaffolds for Alzheimer’s disease through enzyme inhibition, lead optimization, molecular docking and dynamic simulation approaches

Hassan, Mubashir,Abbasi, Muhammad Athar,Aziz-ur-Rehman, Muhammad Athar,Siddiqui, Sabahat Zahra,Shahzadi, Saba,Raza, Hussain,Hussain, Ghulam,Shah, Syed Adnan Ali,Ashraf, Muhamamd,Shahid, Muhammad,Seo, Academic Press 2019 Bioorganic chemistry Vol.91 No.-

<P><B>Abstract</B></P> <P>In the designed research work, a series of 2-furoyl piperazine based sulfonamide derivatives were synthesized as therapeutic agents to target the Alzheimer’s disease. The structures of the newly synthesized compounds were characterized through spectral analysis and their inhibitory potential was evaluated against butyrylcholinesterase (BChE). The cytotoxicity of these sulfonamides was also ascertained through hemolysis of bovine red blood cells. Furthermore, compounds were inspected by Lipinki Rule and their binding profiles against BChE were discerned by molecular docking. The protein fluctuations in docking complexes were recognized by dynamic simulation. From our <I>in vitro</I> and <I>in silico</I> results <B>5c</B>, <B>5j</B> and <B>5k</B> were identified as promising lead compounds for the treatment of targeted disease.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Sulfonamide derivatives were synthesized as therapeutic agents to target the Alzheimer’s disease. </LI> <LI> The inhibitory potential of newly synthesized compounds were evaluated against butyrylcholinesterase (BChE). </LI> <LI> The cytotoxicity of these sulfonamides was also ascertained through hemolysis of bovine red blood cells. </LI> <LI> Computational analysis was performed to check their binding profile against target protein. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Synthesis, characterization and potential applications of Ag@ZnO nanocomposites with S@g-C₃N₄

Ahmad, Naveed,Javed, Mohsin,Qamar, Muhammad A.,Kiran, Umbreen,Shahid, Sammia,Akbar, Muhammad B.,Sher, Mudassar,Amjad, Adnan Techno-Press 2022 Advances in materials research Vol.11 No.3

It includes the synthesis of pristine ZnO nanoparticles and a series of Ag-doped zinc oxide nanoparticles was carried out by reflux method by varying the amount of silver (1, 3, 5, 7 and 9% by mol.). The morphology of these nanoparticles was investigated by SEM, XRD and FT-IR techniques. These techniques show that synthesized particles are homogenous spherical nanoparticles having an average particle size of about 50-100 nm along with some agglomeration. The photocatalytic activity of the ZnO nanoparticles and Ag doped ZnO nanoparticles were investigated via photodegradation of methylene blue (MB) as a standard dye. The data from the photocatalytic activity of these nanoparticles show that 7% Ag-doped ZnO nanoparticles exhibit much enhanced photocatalytic activity as compared to pristine ZnO nanoparticles and other percentages of Ag-doped ZnO nanoparticles. Furthermore, 7% Ag-doped ZnO was made composites with sulfur-doped graphitic carbon nitride by physical mixing method and a series of nanocomposites were made (3.5, 7.5, 25, 50, 75% by weight). It was observed that the 25% composites exhibited better photocatalytic performance than pristine S-g-C 3 N 4 and pure 7% Ag-doped ZnO. Tauc's plot also supports the photodegradation results.

Genome-wide analysis and expression profiling of YUCCA gene family associated with plant vigor in Japanese apricot (prunus mume Sieb. Et zucc)

Hayat Faisal,Bai Yang,Iqbal Shahid,Ma Chengdong,Ali Muhammad Moaaz,Shahid Muhammad Adnan,Hasan Mahmood Ul,Mosa Walid F. A.,Khan Ummara,Xiao Huang,Gao Zhihong 한국원예학회 2023 Horticulture, Environment, and Biotechnology Vol.64 No.5

Indole-3-acetic acid (IAA) is an important plant hormone required for various plant growth and developmental activities. YUCCA proteins are the enzymes for IAA synthesis that catalyze the rate-limiting step. However, the YUCCA gene family in Japanese apricot has not been thoroughly characterized. Here, we investigated the eff ect of rootstocks on scion growth of Japanease apricot and genes involved in auxin biosynthesis ( YUCCA ). Growth characteristics revealed that the height of ‘Longyan’ [ Prunus mume Sieb. et Zucc] plants with P. mume rootstock were signifi cantly shorter than ‘Longyan’ plants with P. persica rootstock. This study isolated 13 PmYUCCA genes from the Japanese apricot genome. Bioinformatics and expression studies were undertaken to investigate the functions and characteristics of YUCCA genes. The physicochemical properties, gene structure, conserved domains, conserved motif, and phylogenetic relationships of YUCCA genes were determined using bioinformatics analysis. Likewise, we analyzed the expression of PmYUCCA genes in Japanese apricot’s leaf and stem-bark (scion). The expression levels of PmYUCCA3 and PmYUCCA5 genes were noticeably lower in the leaves of ‘Longyan’/ P. mume graft combination than that of the ‘Longyan’/ P. persica graft combinations, suggesting their distinct roles in regulating growth vigor. This research explores the genome-wide identifi cation, characterization, and possible relationship between growth vigor and expression profi le analysis of the YUCCA gene family in Japanese apricot.

Synthesis and structure-activity relationship of tyrosinase inhibiting novel bi-heterocyclic acetamides: Mechanistic insights through enzyme inhibition, kinetics and computational studies

Butt, Abdul Rehman Sadiq,Abbasi, Muhammad Athar,Aziz-ur-Rehman, Muhammad Athar,Siddiqui, Sabahat Zahra,Raza, Hussain,Hassan, Mubashir,Shah, Syed Adnan Ali,Shahid, Muhammad,Seo, Sung-Yum Elsevier 2019 Bioorganic chemistry Vol.86 No.-

<P><B>Abstract</B></P> <P>The present research was designed for the selective synthesis of novel bi-heterocyclic acetamides, <B>9a-n</B>, and their tyrosinase inhibition to overwhelm the problem of melanogenesis. The structures of newly synthesized compounds were confirmed by spectral techniques such as <SUP>1</SUP>H NMR, <SUP>13</SUP>C NMR, and EI-MS along with elemental analysis. The inhibitory effects of these bi-heterocyclic acetamides (<B>9a-n</B>) were evaluated against tyrosinase and all these molecules were recognized as potent inhibitors relative to the standard used. The Kinetics mechanism was analyzed by Lineweaver-Burk plots which explored that compound, <B>9h</B>, inhibited tyrosinase competitively by forming an enzyme-inhibitor complex. The inhibition constants K<I> <SUB>i</SUB> </I> calculated from Dixon plots for this compound was 0.0027 µM. The computational study was coherent with the experimental records and these ligands exhibited good binding energy values (kcal/mol). The hemolytic analysis revealed their mild cytotoxicity towards red blood cell membranes and hence, these molecules can be pondered as nontoxic medicinal scaffolds for skin pigmentation and related disorders.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Synthesis of novel bi-heterocyclic acetamides and their tyrosinase inhibition to overwhelm the problem of melanogenesis. </LI> <LI> <I>In vitro</I> and <I>in silico</I> analysis were performed to check their inhibitory potential against tyrosinase enzymes. </LI> <LI> The molecules with small sized methyl group/s at <I>ortho</I>-position/s in aryl part or a flexible phenethyl group, generally inhibited the tyrosinase in an excellent manner. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>