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Shahnaz Perveen - One of the best experts on this subject based on the ideXlab platform.
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Biology-oriented Drug Synthesis (BIODS), in vitro urease inhibitory activity, and in silico studies on ibuprofen derivatives
Molecular Diversity, 2020Co-Authors: Faiza Seraj, Muhammad Taha, Uzma Salar, Khalid Mohammed Khan, Ajmal Khan, Muhammad Ali, Ruqaiya Khalil, Zaheer Ul-haq, Shehryar Hameed, Shahnaz PerveenAbstract:Novel ibuprofen derivatives 1 – 19 including ibuprofen hydrazide 1 , and substituted thiourea derivatives 2 – 19 were synthesized and characterized by EI-MS, FAB-MS, HREI-MS, HRFAB-MS, ^1H-, and ^13C-NMR spectroscopic techniques. The synthetic molecules 1 – 19 were examined for their in vitro urease inhibition and were found to display a diversified degree of inhibitory potential in the range of IC_50 = 2.96–178 μM as compared to the standard thiourea (IC_50 = 21.32 ± 0.22 μM). Out of nineteen, thirteen derivatives 2 – 4 , 6 , 7 , 9 , 11 – 15 , 17 , and 18 demonstrated remarkable inhibitory activity with IC_50 values of 2.96 ± 1.11 to 16.1 ± 1.07 μM, compound 5 exhibited moderate inhibition with IC_50 value of 37.3 ± 0.41 μM, whereas, compounds 1 , 8 , and 10 demonstrated weak inhibition against urease enzyme. Almost all structural features are participating in the activity; however, limited structure–activity relationship was discussed on the basis of different structural features, i.e., different functional groups and their positions at aryl part. In addition, molecular docking study was performed in order to understand the ligands binding interactions with the active site of urease enzyme. Graphic abstract
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Biology-oriented Drug Synthesis (BIODS), in vitro urease inhibitory activity, and in silico study of S-naproxen derivatives.
Bioorganic Chemistry, 2018Co-Authors: Ghulam Mohiuddin, Uzma Salar, Khalid Mohammed Khan, Abdul Wadood, Kanwal, Muhammad Arif Lodhi, Muhammad Riaz, Shahnaz PerveenAbstract:Abstract Current study is based on the biology-oriented Drug Synthesis (BIODS) of S-naproxen (NSAID) derivatives and the evaluation of their urease inhibitory potential. In this regard, a variety of S-naproxen derivatives 2–39 including hydrazide 1, Schiff bases 2–21, aroyl substituted hydrazides 22–24, sulfohydrazides 25–34, 2-mercapto oxadiazole 35, phenacyl substituted 2-mercapto oxadiazoles 36–39 were synthesized under the umbrella of BIODS by simple chemical transformation of its pharmacophoric carboxylic group. Compounds 1–39 were evaluated for in vitro urease inhibitory activity and most of them showed good to moderate inhibitory potential in the range of IC50 = 14.01 ± 0.23–76.43 ± 0.8 µM as compared to standard acetohydroxamic acid (IC50 = 27.0 ± 0.5 µM). Limited structure-activity relationship (SAR) was established in order to rationalize the participation of varying groups (R) in the inhibitory potential of compounds. Molecular docking study on all active compounds was also carried out to decipher the interactions detail of the ligand with the receptors of active site of enzyme.
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biology oriented Drug Synthesis biods in vitro β glucuronidase inhibitory and in silico studies on 2 2 methyl 5 nitro 1h imidazol 1 yl ethyl aryl carboxylate derivatives
European Journal of Medicinal Chemistry, 2017Co-Authors: Uzma Salar, Nor Hadiani Ismail, Shahnaz Perveen, Muhammad Taha, Mehreen Ghufran, Khalid Mohammed Khan, Abdul WadoodAbstract:Abstract Current study is based on the biology-oriented Drug Synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1–26, by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1′-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS, 1H -NMR and 13C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β-glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC50 = 1.20 ± 0.01–60.30 ± 1.40 μM as compared to the standard d -saccharic acid 1,4-lactone (IC50 = 48.38 ± 1.05 μM). Compounds 1, 3, 4, 6, 9–19, and 21–24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies.
Uzma Salar - One of the best experts on this subject based on the ideXlab platform.
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Biology-oriented Drug Synthesis (BIODS), in vitro urease inhibitory activity, and in silico studies on ibuprofen derivatives
Molecular Diversity, 2020Co-Authors: Faiza Seraj, Muhammad Taha, Uzma Salar, Khalid Mohammed Khan, Ajmal Khan, Muhammad Ali, Ruqaiya Khalil, Zaheer Ul-haq, Shehryar Hameed, Shahnaz PerveenAbstract:Novel ibuprofen derivatives 1 – 19 including ibuprofen hydrazide 1 , and substituted thiourea derivatives 2 – 19 were synthesized and characterized by EI-MS, FAB-MS, HREI-MS, HRFAB-MS, ^1H-, and ^13C-NMR spectroscopic techniques. The synthetic molecules 1 – 19 were examined for their in vitro urease inhibition and were found to display a diversified degree of inhibitory potential in the range of IC_50 = 2.96–178 μM as compared to the standard thiourea (IC_50 = 21.32 ± 0.22 μM). Out of nineteen, thirteen derivatives 2 – 4 , 6 , 7 , 9 , 11 – 15 , 17 , and 18 demonstrated remarkable inhibitory activity with IC_50 values of 2.96 ± 1.11 to 16.1 ± 1.07 μM, compound 5 exhibited moderate inhibition with IC_50 value of 37.3 ± 0.41 μM, whereas, compounds 1 , 8 , and 10 demonstrated weak inhibition against urease enzyme. Almost all structural features are participating in the activity; however, limited structure–activity relationship was discussed on the basis of different structural features, i.e., different functional groups and their positions at aryl part. In addition, molecular docking study was performed in order to understand the ligands binding interactions with the active site of urease enzyme. Graphic abstract
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Biology-oriented Drug Synthesis (BIODS), Structural Characterization and Bioactivities of Novel Albendazole Derivatives
Letters in Drug Design & Discovery, 2019Co-Authors: Momin Khan, Uzma Salar, Khalid Mohammed Khan, Shahid Khan, Gauhar Rehman, I. A. KhanAbstract:Background: Albendazole is a Drug, belongs to the family of benzimidazole, and used as an anthelmintic agent in both human and veterinary medicine. It is marketed as Albenza which is used for the treatment of a variety of parasitic worm infestations such as roundworms, tapeworms, and flukes. In recent past, we have reported various classes of compounds as anti-glycating agents, in continuation of Biology-oriented Drug Synthesis (BIODS), seventeen albendazole derivatives 2-18 were synthesized evaluated for yeast glucose uptake activity. Methods: In the present study, Albendazole (2 g, 7.5 mmol), potassium hydroxide (3 g) were dissolved in ethanol (50 mL) into a 250 mL round-bottomed flask and refluxed for 48 h. TLC (ethyl acetate: hexane, 6:4) was monitored in order to check the reaction progress. After completion, the reaction mixture was dried under air and washed with an excess of distilled water. Precipitates were dried and crystallized from ethanol. The product was characterized by EI-MS and 1H-NMR. Results: Our present study showed that all compounds showed a varying degree of yeast glucose uptake activity ranging between IC50 = 51.41-258.40 µM, compared with standard metronidazole (IC50 = 41.86 ± 0.09 µM). This study has identified a series of potential leads for anti-glycating agents. Conclusion: Biology-oriented Drug Synthesis and in vitro yeast glucose uptake activity of albendazole derivatives gave rise to a number of lead molecule such as 3 (IC50 = 59.37 ± 0.26 µM), 5 (IC50 = 59.70 ± 0.32 µM), 6 (IC50 = 60.78 ± 0.54 µM), 8 (IC50 = 54.61 ± 0.20 µM), 16 (IC50 = 56.57 ± 0.04 µM) and 14 (IC50 = 51.41 ± 1.25 µM).
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Atenolol thiourea hybrid as potent urease inhibitors: Design, biology-oriented Drug Synthesis, inhibitory activity screening, and molecular docking studies.
Bioorganic Chemistry, 2019Co-Authors: Sana Wahid, Uzma Salar, Khalid Mohammed Khan, Abdul Wadood, Kanwal, Sajid Jahangir, Muhammad Ali Versiani, Muhammad Ashraf, Urva Farzand, Ashfaq-ur-rehamanAbstract:Abstract Current research deals with the biology-oriented Drug Synthesis (BIODS) of twenty-three new thiourea analogs of pharmacologically important Drug atenolol which is a well-known medicine to treat hypertension as well as cardiovascular diseases (CVDs). Structural characterization of all compounds was done by various spectroscopic techniques. Compounds 1–23 were subjected for urease inhibitory activity in vitro. Screening results revealed that whole library was found to be active having IC50 ranges from 11.73 ± 0.28 to 212.24 ± 0.42 µM. It is noteworthy that several derivatives including 3 (IC50 = 21.65 ± 0.31 µM), 8 (IC50 = 19.26 ± 0.42 µM), 9 (IC50 = 21.27 ± 0.25 µM), 12 (IC50 = 21.52 ± 0.42 µM), 17 (IC50 = 19.26 ± 0.42 µM), 20 (IC50 = 16.78 ± 0.34 µM), and 22 (IC50 = 11.73 ± 0.28 µM) showed excellent inhibitory potential than parent atenolol (IC50 = 64.36 ± 0.19 µM) and standard thiourea (IC50 = 21.74 ± 1.76 µM). A most probable structure–activity relationship (SAR) was anticipated by observing varying degree of inhibitory potential given by compounds. However, molecular insights regarding the binding mode of atenolol thiourea analogs within the active pocket of urease enzyme was rationalized by molecular docking studies.
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Biology-oriented Drug Synthesis (BIODS), in vitro urease inhibitory activity, and in silico study of S-naproxen derivatives.
Bioorganic Chemistry, 2018Co-Authors: Ghulam Mohiuddin, Uzma Salar, Khalid Mohammed Khan, Abdul Wadood, Kanwal, Muhammad Arif Lodhi, Muhammad Riaz, Shahnaz PerveenAbstract:Abstract Current study is based on the biology-oriented Drug Synthesis (BIODS) of S-naproxen (NSAID) derivatives and the evaluation of their urease inhibitory potential. In this regard, a variety of S-naproxen derivatives 2–39 including hydrazide 1, Schiff bases 2–21, aroyl substituted hydrazides 22–24, sulfohydrazides 25–34, 2-mercapto oxadiazole 35, phenacyl substituted 2-mercapto oxadiazoles 36–39 were synthesized under the umbrella of BIODS by simple chemical transformation of its pharmacophoric carboxylic group. Compounds 1–39 were evaluated for in vitro urease inhibitory activity and most of them showed good to moderate inhibitory potential in the range of IC50 = 14.01 ± 0.23–76.43 ± 0.8 µM as compared to standard acetohydroxamic acid (IC50 = 27.0 ± 0.5 µM). Limited structure-activity relationship (SAR) was established in order to rationalize the participation of varying groups (R) in the inhibitory potential of compounds. Molecular docking study on all active compounds was also carried out to decipher the interactions detail of the ligand with the receptors of active site of enzyme.
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biology oriented Drug Synthesis biods in vitro β glucuronidase inhibitory and in silico studies on 2 2 methyl 5 nitro 1h imidazol 1 yl ethyl aryl carboxylate derivatives
European Journal of Medicinal Chemistry, 2017Co-Authors: Uzma Salar, Nor Hadiani Ismail, Shahnaz Perveen, Muhammad Taha, Mehreen Ghufran, Khalid Mohammed Khan, Abdul WadoodAbstract:Abstract Current study is based on the biology-oriented Drug Synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1–26, by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1′-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS, 1H -NMR and 13C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β-glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC50 = 1.20 ± 0.01–60.30 ± 1.40 μM as compared to the standard d -saccharic acid 1,4-lactone (IC50 = 48.38 ± 1.05 μM). Compounds 1, 3, 4, 6, 9–19, and 21–24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies.
Khalid Mohammed Khan - One of the best experts on this subject based on the ideXlab platform.
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Biology-oriented Drug Synthesis (BIODS), in vitro urease inhibitory activity, and in silico studies on ibuprofen derivatives
Molecular Diversity, 2020Co-Authors: Faiza Seraj, Muhammad Taha, Uzma Salar, Khalid Mohammed Khan, Ajmal Khan, Muhammad Ali, Ruqaiya Khalil, Zaheer Ul-haq, Shehryar Hameed, Shahnaz PerveenAbstract:Novel ibuprofen derivatives 1 – 19 including ibuprofen hydrazide 1 , and substituted thiourea derivatives 2 – 19 were synthesized and characterized by EI-MS, FAB-MS, HREI-MS, HRFAB-MS, ^1H-, and ^13C-NMR spectroscopic techniques. The synthetic molecules 1 – 19 were examined for their in vitro urease inhibition and were found to display a diversified degree of inhibitory potential in the range of IC_50 = 2.96–178 μM as compared to the standard thiourea (IC_50 = 21.32 ± 0.22 μM). Out of nineteen, thirteen derivatives 2 – 4 , 6 , 7 , 9 , 11 – 15 , 17 , and 18 demonstrated remarkable inhibitory activity with IC_50 values of 2.96 ± 1.11 to 16.1 ± 1.07 μM, compound 5 exhibited moderate inhibition with IC_50 value of 37.3 ± 0.41 μM, whereas, compounds 1 , 8 , and 10 demonstrated weak inhibition against urease enzyme. Almost all structural features are participating in the activity; however, limited structure–activity relationship was discussed on the basis of different structural features, i.e., different functional groups and their positions at aryl part. In addition, molecular docking study was performed in order to understand the ligands binding interactions with the active site of urease enzyme. Graphic abstract
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Biology-oriented Drug Synthesis (BIODS), Structural Characterization and Bioactivities of Novel Albendazole Derivatives
Letters in Drug Design & Discovery, 2019Co-Authors: Momin Khan, Uzma Salar, Khalid Mohammed Khan, Shahid Khan, Gauhar Rehman, I. A. KhanAbstract:Background: Albendazole is a Drug, belongs to the family of benzimidazole, and used as an anthelmintic agent in both human and veterinary medicine. It is marketed as Albenza which is used for the treatment of a variety of parasitic worm infestations such as roundworms, tapeworms, and flukes. In recent past, we have reported various classes of compounds as anti-glycating agents, in continuation of Biology-oriented Drug Synthesis (BIODS), seventeen albendazole derivatives 2-18 were synthesized evaluated for yeast glucose uptake activity. Methods: In the present study, Albendazole (2 g, 7.5 mmol), potassium hydroxide (3 g) were dissolved in ethanol (50 mL) into a 250 mL round-bottomed flask and refluxed for 48 h. TLC (ethyl acetate: hexane, 6:4) was monitored in order to check the reaction progress. After completion, the reaction mixture was dried under air and washed with an excess of distilled water. Precipitates were dried and crystallized from ethanol. The product was characterized by EI-MS and 1H-NMR. Results: Our present study showed that all compounds showed a varying degree of yeast glucose uptake activity ranging between IC50 = 51.41-258.40 µM, compared with standard metronidazole (IC50 = 41.86 ± 0.09 µM). This study has identified a series of potential leads for anti-glycating agents. Conclusion: Biology-oriented Drug Synthesis and in vitro yeast glucose uptake activity of albendazole derivatives gave rise to a number of lead molecule such as 3 (IC50 = 59.37 ± 0.26 µM), 5 (IC50 = 59.70 ± 0.32 µM), 6 (IC50 = 60.78 ± 0.54 µM), 8 (IC50 = 54.61 ± 0.20 µM), 16 (IC50 = 56.57 ± 0.04 µM) and 14 (IC50 = 51.41 ± 1.25 µM).
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Atenolol thiourea hybrid as potent urease inhibitors: Design, biology-oriented Drug Synthesis, inhibitory activity screening, and molecular docking studies.
Bioorganic Chemistry, 2019Co-Authors: Sana Wahid, Uzma Salar, Khalid Mohammed Khan, Abdul Wadood, Kanwal, Sajid Jahangir, Muhammad Ali Versiani, Muhammad Ashraf, Urva Farzand, Ashfaq-ur-rehamanAbstract:Abstract Current research deals with the biology-oriented Drug Synthesis (BIODS) of twenty-three new thiourea analogs of pharmacologically important Drug atenolol which is a well-known medicine to treat hypertension as well as cardiovascular diseases (CVDs). Structural characterization of all compounds was done by various spectroscopic techniques. Compounds 1–23 were subjected for urease inhibitory activity in vitro. Screening results revealed that whole library was found to be active having IC50 ranges from 11.73 ± 0.28 to 212.24 ± 0.42 µM. It is noteworthy that several derivatives including 3 (IC50 = 21.65 ± 0.31 µM), 8 (IC50 = 19.26 ± 0.42 µM), 9 (IC50 = 21.27 ± 0.25 µM), 12 (IC50 = 21.52 ± 0.42 µM), 17 (IC50 = 19.26 ± 0.42 µM), 20 (IC50 = 16.78 ± 0.34 µM), and 22 (IC50 = 11.73 ± 0.28 µM) showed excellent inhibitory potential than parent atenolol (IC50 = 64.36 ± 0.19 µM) and standard thiourea (IC50 = 21.74 ± 1.76 µM). A most probable structure–activity relationship (SAR) was anticipated by observing varying degree of inhibitory potential given by compounds. However, molecular insights regarding the binding mode of atenolol thiourea analogs within the active pocket of urease enzyme was rationalized by molecular docking studies.
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Biology-oriented Drug Synthesis (BIODS), in vitro urease inhibitory activity, and in silico study of S-naproxen derivatives.
Bioorganic Chemistry, 2018Co-Authors: Ghulam Mohiuddin, Uzma Salar, Khalid Mohammed Khan, Abdul Wadood, Kanwal, Muhammad Arif Lodhi, Muhammad Riaz, Shahnaz PerveenAbstract:Abstract Current study is based on the biology-oriented Drug Synthesis (BIODS) of S-naproxen (NSAID) derivatives and the evaluation of their urease inhibitory potential. In this regard, a variety of S-naproxen derivatives 2–39 including hydrazide 1, Schiff bases 2–21, aroyl substituted hydrazides 22–24, sulfohydrazides 25–34, 2-mercapto oxadiazole 35, phenacyl substituted 2-mercapto oxadiazoles 36–39 were synthesized under the umbrella of BIODS by simple chemical transformation of its pharmacophoric carboxylic group. Compounds 1–39 were evaluated for in vitro urease inhibitory activity and most of them showed good to moderate inhibitory potential in the range of IC50 = 14.01 ± 0.23–76.43 ± 0.8 µM as compared to standard acetohydroxamic acid (IC50 = 27.0 ± 0.5 µM). Limited structure-activity relationship (SAR) was established in order to rationalize the participation of varying groups (R) in the inhibitory potential of compounds. Molecular docking study on all active compounds was also carried out to decipher the interactions detail of the ligand with the receptors of active site of enzyme.
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biology oriented Drug Synthesis biods in vitro β glucuronidase inhibitory and in silico studies on 2 2 methyl 5 nitro 1h imidazol 1 yl ethyl aryl carboxylate derivatives
European Journal of Medicinal Chemistry, 2017Co-Authors: Uzma Salar, Nor Hadiani Ismail, Shahnaz Perveen, Muhammad Taha, Mehreen Ghufran, Khalid Mohammed Khan, Abdul WadoodAbstract:Abstract Current study is based on the biology-oriented Drug Synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1–26, by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1′-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS, 1H -NMR and 13C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β-glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC50 = 1.20 ± 0.01–60.30 ± 1.40 μM as compared to the standard d -saccharic acid 1,4-lactone (IC50 = 48.38 ± 1.05 μM). Compounds 1, 3, 4, 6, 9–19, and 21–24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies.
Abdul Wadood - One of the best experts on this subject based on the ideXlab platform.
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Atenolol thiourea hybrid as potent urease inhibitors: Design, biology-oriented Drug Synthesis, inhibitory activity screening, and molecular docking studies.
Bioorganic Chemistry, 2019Co-Authors: Sana Wahid, Uzma Salar, Khalid Mohammed Khan, Abdul Wadood, Kanwal, Sajid Jahangir, Muhammad Ali Versiani, Muhammad Ashraf, Urva Farzand, Ashfaq-ur-rehamanAbstract:Abstract Current research deals with the biology-oriented Drug Synthesis (BIODS) of twenty-three new thiourea analogs of pharmacologically important Drug atenolol which is a well-known medicine to treat hypertension as well as cardiovascular diseases (CVDs). Structural characterization of all compounds was done by various spectroscopic techniques. Compounds 1–23 were subjected for urease inhibitory activity in vitro. Screening results revealed that whole library was found to be active having IC50 ranges from 11.73 ± 0.28 to 212.24 ± 0.42 µM. It is noteworthy that several derivatives including 3 (IC50 = 21.65 ± 0.31 µM), 8 (IC50 = 19.26 ± 0.42 µM), 9 (IC50 = 21.27 ± 0.25 µM), 12 (IC50 = 21.52 ± 0.42 µM), 17 (IC50 = 19.26 ± 0.42 µM), 20 (IC50 = 16.78 ± 0.34 µM), and 22 (IC50 = 11.73 ± 0.28 µM) showed excellent inhibitory potential than parent atenolol (IC50 = 64.36 ± 0.19 µM) and standard thiourea (IC50 = 21.74 ± 1.76 µM). A most probable structure–activity relationship (SAR) was anticipated by observing varying degree of inhibitory potential given by compounds. However, molecular insights regarding the binding mode of atenolol thiourea analogs within the active pocket of urease enzyme was rationalized by molecular docking studies.
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Biology-oriented Drug Synthesis (BIODS), in vitro urease inhibitory activity, and in silico study of S-naproxen derivatives.
Bioorganic Chemistry, 2018Co-Authors: Ghulam Mohiuddin, Uzma Salar, Khalid Mohammed Khan, Abdul Wadood, Kanwal, Muhammad Arif Lodhi, Muhammad Riaz, Shahnaz PerveenAbstract:Abstract Current study is based on the biology-oriented Drug Synthesis (BIODS) of S-naproxen (NSAID) derivatives and the evaluation of their urease inhibitory potential. In this regard, a variety of S-naproxen derivatives 2–39 including hydrazide 1, Schiff bases 2–21, aroyl substituted hydrazides 22–24, sulfohydrazides 25–34, 2-mercapto oxadiazole 35, phenacyl substituted 2-mercapto oxadiazoles 36–39 were synthesized under the umbrella of BIODS by simple chemical transformation of its pharmacophoric carboxylic group. Compounds 1–39 were evaluated for in vitro urease inhibitory activity and most of them showed good to moderate inhibitory potential in the range of IC50 = 14.01 ± 0.23–76.43 ± 0.8 µM as compared to standard acetohydroxamic acid (IC50 = 27.0 ± 0.5 µM). Limited structure-activity relationship (SAR) was established in order to rationalize the participation of varying groups (R) in the inhibitory potential of compounds. Molecular docking study on all active compounds was also carried out to decipher the interactions detail of the ligand with the receptors of active site of enzyme.
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biology oriented Drug Synthesis biods in vitro β glucuronidase inhibitory and in silico studies on 2 2 methyl 5 nitro 1h imidazol 1 yl ethyl aryl carboxylate derivatives
European Journal of Medicinal Chemistry, 2017Co-Authors: Uzma Salar, Nor Hadiani Ismail, Shahnaz Perveen, Muhammad Taha, Mehreen Ghufran, Khalid Mohammed Khan, Abdul WadoodAbstract:Abstract Current study is based on the biology-oriented Drug Synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1–26, by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1′-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS, 1H -NMR and 13C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β-glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC50 = 1.20 ± 0.01–60.30 ± 1.40 μM as compared to the standard d -saccharic acid 1,4-lactone (IC50 = 48.38 ± 1.05 μM). Compounds 1, 3, 4, 6, 9–19, and 21–24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies.
Muhammad Taha - One of the best experts on this subject based on the ideXlab platform.
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Biology-oriented Drug Synthesis (BIODS), in vitro urease inhibitory activity, and in silico studies on ibuprofen derivatives
Molecular Diversity, 2020Co-Authors: Faiza Seraj, Muhammad Taha, Uzma Salar, Khalid Mohammed Khan, Ajmal Khan, Muhammad Ali, Ruqaiya Khalil, Zaheer Ul-haq, Shehryar Hameed, Shahnaz PerveenAbstract:Novel ibuprofen derivatives 1 – 19 including ibuprofen hydrazide 1 , and substituted thiourea derivatives 2 – 19 were synthesized and characterized by EI-MS, FAB-MS, HREI-MS, HRFAB-MS, ^1H-, and ^13C-NMR spectroscopic techniques. The synthetic molecules 1 – 19 were examined for their in vitro urease inhibition and were found to display a diversified degree of inhibitory potential in the range of IC_50 = 2.96–178 μM as compared to the standard thiourea (IC_50 = 21.32 ± 0.22 μM). Out of nineteen, thirteen derivatives 2 – 4 , 6 , 7 , 9 , 11 – 15 , 17 , and 18 demonstrated remarkable inhibitory activity with IC_50 values of 2.96 ± 1.11 to 16.1 ± 1.07 μM, compound 5 exhibited moderate inhibition with IC_50 value of 37.3 ± 0.41 μM, whereas, compounds 1 , 8 , and 10 demonstrated weak inhibition against urease enzyme. Almost all structural features are participating in the activity; however, limited structure–activity relationship was discussed on the basis of different structural features, i.e., different functional groups and their positions at aryl part. In addition, molecular docking study was performed in order to understand the ligands binding interactions with the active site of urease enzyme. Graphic abstract
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biology oriented Drug Synthesis biods in vitro β glucuronidase inhibitory and in silico studies on 2 2 methyl 5 nitro 1h imidazol 1 yl ethyl aryl carboxylate derivatives
European Journal of Medicinal Chemistry, 2017Co-Authors: Uzma Salar, Nor Hadiani Ismail, Shahnaz Perveen, Muhammad Taha, Mehreen Ghufran, Khalid Mohammed Khan, Abdul WadoodAbstract:Abstract Current study is based on the biology-oriented Drug Synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1–26, by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1′-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS, 1H -NMR and 13C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β-glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC50 = 1.20 ± 0.01–60.30 ± 1.40 μM as compared to the standard d -saccharic acid 1,4-lactone (IC50 = 48.38 ± 1.05 μM). Compounds 1, 3, 4, 6, 9–19, and 21–24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies.
