Flurbiprofen–antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling

Ashraf, Zaman,Alamgeer,Kanwal, Munazza,Hassan, Mubashir,Abdullah, Sahar,Waheed, Mamuna,Ahsan, Haseeb,Kim, Song Ja Dove Medical Press 2016 Drug design, development and therapy Vol.10 No.-

<P>Flurbiprofen–antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (–COOH) was temporarily masked by esterification with phenolic –OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (<I>P</I><0.001) reduced the inflammation against carrageenan and egg albumin-induced paw edema at 4 hours of study. The reduction in the size of the inflamed paw showed that most of the compounds inhibited the later phase of inflammation. The prodrug 2-oxo-2<I>H</I>-chromen-7-yl-2-(2-fluorobiphenyl-4-yl)propanoate (<B>4b</B>) showed significant reduction in paw licking with percentage inhibition of 58%. It also exhibited higher analgesic activity, reducing the number of writhes with a percentage of 75%, whereas flurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer’s yeast-induced pyrexia model, and significant (<I>P</I><0.001) reduction in rectal temperature was shown by all prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities with reduced GI adverse effects than the parent drug.</P>

Synthesis, Bioevaluation and Molecular Dynamic Simulation Studies of Dexibuprofen–Antioxidant Mutual Prodrugs

Ashraf, Zaman,Alamgeer,,Rasool, Raqiqatur,Hassan, Mubashir,Ahsan, Haseeb,Afzal, Samina,Afzal, Khurram,Cho, Hongsik,Kim, Song Ja,Zhang, Ge,Lu, Aiping MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.12

<P>Dexibuprofen–antioxidant conjugates were synthesized with the aim to reduce its gastrointestinal effects. The esters analogs of dexibuprofen <B>5a</B>–<B>c</B> were obtained by reacting its –COOH group with chloroacetyl derivatives <B>3a</B>–<B>c</B>. The in vitro hydrolysis data confirmed that synthesized prodrugs <B>5a</B>–<B>c</B> were stable in stomach while undergo significant hydrolysis in 80% human plasma and thus release free dexibuprofen. The minimum reversion was observed at pH 1.2 suggesting that prodrugs are less irritating to stomach than dexibuprofen. The anti-inflammatory activity of <B>5c</B> (<I>p</I> < 0.001) is more significant than the parent dexibuprofen. The prodrug <B>5c</B> produced maximum inhibition (42.06%) of paw-edema against egg-albumin induced inflammation in mice. Anti-pyretic effects in mice indicated that prodrugs <B>5a</B> and <B>5b</B> showed significant inhibition of pyrexia (<I>p</I> < 0.001). The analgesic activity of <B>5a</B> is more pronounced compared to other synthesized prodrugs. The mean percent inhibition indicated that the prodrug <B>5a</B> was more active in decreasing the number of writhes induced by acetic acid than standard dexibuprofen. The ulcerogenic activity results assured that synthesized prodrugs produce less gastrointestinal adverse effects than dexibuprofen. The ex vivo antiplatelet aggregation activity results also confirmed that synthesized prodrugs are less irritant to gastrointestinal mucosa than the parent dexibuprofen. Molecular docking analysis showed that the prodrugs <B>5a</B>–<B>c</B> interacts with the residues present in active binding sites of target protein. The stability of drug–target complexes is verified by molecular dynamic simulation study. It exhibited that synthesized prodrugs formed stable complexes with the COX-2 protein thus support our wet lab results. It is therefore concluded that the synthesized prodrugs have promising pharmacological activities with reduced gastrointestinal adverse effects than the parent drug.</P>

Development of UV Protective, Superhydrophobic and Antibacterial Textiles Using ZnO and TiO2 Nanoparticles

Muhammad Zaman Khan,Vijay Baheti,Munir Ashraf,Tanveer Hussain,Azam Ali,Amjed Javid,Abdur Rehman 한국섬유공학회 2018 Fibers and polymers Vol.19 No.8

In this research work, multifunctional cotton fabric comprising of UV protection, superhydrophobicity and antibacterial activity has been developed using facile pad-dry-cure method. In the first step, the concentration of repellent chemical has been optimized. Then, formulations containing nanoparticles of ZnO or TiO2 along with optimized concentration of repellent chemical and organic-inorganic binder have been applied to cotton fabric followed by the evaluation of functional properties. The surface morphology and elemental composition of treated fabric has been characterized through SEM and EDX, respectively. The treated samples have shown promising UV protection, superhydrophobicity and antibacterial properties durable upto 20 washing cycles.

Development of highly potent melanogenesis inhibitor by in vitro, in vivo and computational studies

Abbas, Qamar,Ashraf, Zaman,Hassan, Mubashir,Nadeem, Humaira,Latif, Muhammad,Afzal, Samina,Seo, Sung-Yum Dove Medical Press 2017 Drug design, development and therapy Vol.11 No.-

<P>The present work describes the synthesis of few hydroxylated amide derivatives as melanogenesis inhibitors. In vitro, in vivo and computational studies proved that compound <B>6d</B> is a highly potent melanogenesis inhibitor compared to standard kojic acid. The title amides <B>4a</B>–<B>e</B> and <B>6a</B>–<B>e</B> were synthesized following simple reaction routes with excellent yields. Most of the synthesized compounds exhibited good mushroom tyrosinase inhibitory activity, but compound <B>6d</B> showed excellent activity (IC<SUB>50</SUB> 0.15 µM) compared to standard kojic acid (IC<SUB>50</SUB> 16.69 µM). Lineweaver–Burk plots were used for the determination of kinetic mechanism, and it was found that compounds <B>4c</B> and <B>6d</B> showed non-competitive inhibition while <B>6a</B> and <B>6b</B> showed mixed-type inhibition. The kinetic mechanism further revealed that compound <B>6d</B> formed irreversible complex with the target enzyme tyrosinase. The <I>Ki</I> values determined for compounds <B>4c</B>, <B>6a</B>, <B>6b</B> and <B>6d</B> are 0.188, 0.84, 2.20 and 0.217 µM respectively. Results of human tyrosinase inhibitory activity in A375 human melanoma cells showed that compound <B>6d</B> exhibited 91.9% inhibi-tory activity at a concentration of 50 µg/mL. In vivo cytotoxicity evaluation of compound <B>6d</B> in zebrafish embryos showed that it is non-toxic to zebrafish. Melanin depigmentation assay performed in zebrafish indicated that compound <B>6d</B> possessed greater potential in decreasing melanin contents compared to kojic acid at the same concentration. Computational studies also supported the wet lab findings as compound <B>6d</B> showed a highest binding affinity with the target protein (PDBID: 2Y9X) with a binding energy value of −7.90 kcal/mol. Molecular dynamic simulation studies also proved that amide <B>6d</B> formed the most stable complex with tyrosinase. Based upon our in vitro, in vivo and computational studies, we propose that compound <B>6d</B> is a promising candidate for the development of safe cosmetic agent.</P>

Synthesis and enzyme inhibitory kinetics of some novel 3-(substituted benzoyl)-2-thioxoimidazolidin-4-one derivatives as α-glucosidase/α-amylase inhibitors

Qamar, Rabia,Saeed, Aamer,Saeed, Maria,Shah, Babar Hussain,Ashraf, Zaman,Abbas, Qamar,Seo, Sung Yum Springer-Verlag 2018 Medicinal Chemistry Research Vol.27 No.5

Institutional Information Management and Automation System

M.Ahmad Nawaz Ul Ghani,Taimour Nazar,Syed Zeeshan Hussain Shah Gellani,Zaman Ashraf International Journal of Computer ScienceNetwork S 2023 International journal of computer science and netw Vol.23 No.8

World is moving towards digitization at a rapid pace, so the enterprises have developed information systems for management of their business. Empowering educational institutes with information systems are become very important and vital. Doing everything manually is very difficult for students, teachers and staff. Information system can enhance their efficiency and save a lot of time; this research proposed system will solve this issue by providing services like class room reservation, e-library facility, online submission etc. in a secured environment. Up till now limited attention has been paid to utilize robots and drones for automation inside educational institutes. Our proposed system incorporates robots and drones to fill this gap in automation being used in institutes. Through this research, the aim is to improve the efficiency of learning and services in educational institutions or universities.