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Home > Synthesis of Some N4-Substituted Isatins-3-Thiosemicarbazones and Their Transition Metal Complexes As Potential Bioactive Agents.

Synthesis of Some N4-Substituted Isatins-3-Thiosemicarbazones and Their Transition Metal Complexes As Potential Bioactive Agents.

Thesis Info

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Author

Khan, Nazia

Program

PhD

Institute

Bahauddin Zakariya University

City

Multan

Province

KPK

Country

Pakistan

Thesis Completing Year

2019

Thesis Completion Status

Completed

Subject

Biochemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/13363/1/Nazia%20Khan_Chem_2019_BZU_PRR.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727496570

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The focus of this thesis is on the synthesis and in vitro biological testing of some target N4- substituted isatin-3-thiosemicarbazones and their transition metal complexes. Thus, three series of N4-benzyl substituted isatin-3-thiosemicarbazones (19-33), (34- 48) and (49-63) were synthesized by condensing isatin, 5-nitroisatin and 5-chloroisatin, respectively, with the appropriate N-substituted thiosemicarbazides. All the synthesized thiosemicarbazones (19-63) were characterized by means of their analytical (CHN) and spectral (IR, 1H-NMR, 13C-NMR, EIMS) data and tested for the selected biological properties i.e. antiurease, phytotoxic, cytotoxic, anticarbonic anhydrase and antiglycation activities. All the synthetic thiosemicarbazones (19-63) proved to be highly potent inhibitors of urease, displaying excellent inhibitory activity (IC50 = 0.87 ± 0.25 − 11.23 ± 0.19 µM) even better than the reference inhibitor, thiourea (IC50 = 22.3 ± 1.06 µM) used in the assay. In phytotoxicity assay, 33 out of 45 thiosemicarbazones tested i.e. (19-22), (25), (26), (28-30), (32), (33), (34-40), (42-44), (46-48), (51), (52), (56-61) and (63) appeared to be active, exhibiting weak or non-significant (5-100%) growth inhibition of Lemna aequinocitalis at 1000 or 500 µg/mL concentrations in comparison to paraquat (the standard herbicide), which showed 100% plant growth inhibition at 0.015 µg/mL concentration. In the brine shrimp (Artemia salina) lethality bioassay, only 4 compounds i.e. (20), (28), (33) and (42) were found to be active, demonstrating cytotoxic activity with LD50 values 3.63 × 10-5, 2.90 × 10-5, 2.31 × 10-4 and 2.55 × 10-5 M, respectively. The remaining compounds gave LD50 values greater than 2.36 × 10-4 − 3.22 × 10-4 M and were, therefore, considered to be almost inactive. On the other hand, in the carbonic anhydrase (CA-II) inhibition bioassay, all the trial compounds (19-63) showed less than 50% of enzymatic inhibition and thus were considered to be inactive. However, in the antiglycation activity assay, 21 out of 45 compounds tested i.e. (20-22), (24), (26), (28), (29), (34), (36), (39), (45), (47), (48), (50), (51), (56-59), (61) and (62) proved to be potent inhibitors of glycation, demonstrating inhibition with IC50 values ranging from 114.51 ± 1.08 to 643.80 ± 5.80 µM. Of these, (21), (22), (26), (28), (29), (34), (36), (51), (56-58) and (62) exhibited superb inhibitory activity (IC50 = 114.51 ± 1.08 – 241.90 ± 1.97 µM) even better than the reference inhibitor, rutin (294.50 ± 1.50 µM) and thus may act as convincing leads for further studies. The synthetic thiosemicarbazones (19), (21), (22), (24-31), (34-37), (39-42), (44-46) and (48) were used as ligands for synthesizing their Cu(II) complexes. All the synthesized metal complexes (64-86) were characterized by means of their analytical (CHN), spectral (IR, R (Raman), UV-Vis), magnetic moments, thermal and molar conductance data, and evaluated for the selected biological properties viz. antiurease, anticarbonic anhydrase and antiglycation activities. In antiurease assay, coordination of all the thiosemicarbazone ligands to metal ions was found to lead to decrement in the enzyme inhibitory activity that they possessed. Relatively, extensive decrease occurred in the cases of (65), (67), (68), (71), (73), (76-81) and (84). On the contrary, in CA inhibition bioassay, coordination of the ligands to metal ions was found to give rise to induction of enzyme inhibitory activity in certain cases. For example, the metal complexes (66), (72-76), (80) and (83-86) exhibited promising enzymatic inhibition with IC50 values 5.9 ± 0.00 − 21.26 ± 0.35 µM in contrast to the corresponding ligands (22), (29-31), (34), (35), (40), (44-46) and (48), which displayed less than 50% (i.e. from − 9.3 to 33.1%) inhibition of the enzyme and thus considered to be inactive. Similarly, the coordination of thiosemicarbazone ligands to metal ions was found to bring about either induction or enhancement of antiglycation activity. For example, the metal complexes (64), (68), (70), (73), (74), (76), (78), (80-83) and (85) showed excellent activity with IC50 values ranging from 105.74 ± 3.1 to 247.06 ± 1.75 µM as compared to the relevant ligands (19), (25), (27), (30), (31), (35), (37), (40-43) and (46), which demonstrated less than 50% (i.e. 10.32−40.98 %) inhibition of glycation. Similarly, the metal complexes (65-67), (69), (71), (72), (75), (77), (79) and (84) displayed markedly enhanced antiglycation activity in comparison to the respective ligands (21), (22), (24), (26), (28), (29), (34), (36), (39) and (45) (IC50 values 94.64 ± 0.99 − 135.20 ± 1.87 vs. 209.87 ± 0.37 − 522.68 ± 9.1 µM).
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اعزازات

اعزازات:

                ناطق کا پہلا شعری مجموعہ’’بے یقین بستیوں میں‘‘رسالہ’’آج‘‘ میں کراچی سے 2010ء میں شائع ہوا۔ان کی نظموں کو بہت سراہا گیااس لیے اس مجموعہ کو ’’یو بی ایل‘‘اعزاز کیلئے بھی نامزد کیا گیا۔ان کا پہلا افسانوی مجموعہ ’’قائم دین‘‘ آکسفورڈ سے چھپااور نثر میں ان کے اس پہلے افسانوی مجموعے کو ’’یوبی ایل‘‘ایوارڈ سے نوازا گیا۔

رحمۃ للعالمينﷺ کے غیر مسلموں سے معاملات قرآن و سیرت طیبہ کی روشنی میں

Dealings of the Holy Prophet (S.A.W) with non-Muslim show that Islam is the religion of peace, brotherhood, religious tolerance, independence and humanity. Before the spread of Islam the conversations and dealings of the Holy Prophet with non-Muslims forced them to call him Al-Sadiq and Al-Ameen. Sympathy and tolerance in clandestine and public preaching, the style of letters to non-Muslim empires, the dialogues with non-Muslim delegations in Madani era, the orders given for the safety of their wealth, belongings and their life, the tolerance, forgiveness and prayers for the enemies, the good behavior with the non-Muslim prisoners, even when Muslims got dominance over non-Muslims at the time of the conquest of Makkah, the common pardon given by Holy Prophet (S.A.W) are the true example that Islam preaches peace. The attitude of Sahaba-e-Karam (R.A) and the liberty of rights given to Non-Muslims by them- no religion and no community of the World can give this example. The people responsible for maintaining the peace of the world and brotherhood should see how Muslims are treated all over the world? Muslims had given to non-Muslim permission to practice their religious festivities freely and even to wear any type of clothes. The ban of Hijab in France, the punishment of innocent Dr. Afia Siddiqui, the Egyptian pregnant woman (Marwa Sharbeney) had been mercilessly assassinated and her husband injured by knives in the court of Germany because of Hijab, the discussions going on to restrict the domes of Mosques and Adhan (Call to prayer) in Switzerland, the insult of the Holy Quran by Pope Terry John, of Florida, the disrespect of Holy Prophet (S.A.W) etc are the questions awaiting answers from West and United Nation. Islam promotes of peace, equality and religious freedom. It also invites non-Muslims to come and sit on a platform and discuss these problems for the sake of worldly peace to end the religious hatred and to form true peace in the world.

Toxicological Studies of Recent Conventional Insecticides and Fungicide Groups in Comparison With Azadirachta Indica Neem Leaf Extract Against Adult Earthworm, Pheretima Posthuma With Reference to Effect on Proteins & Enzymes

The current study, illustrate the toxicity of five pesticides i.e. sulfoxaflor, nitenpyram, spinetoram, azoxystrobin and neem leaf extract against imago (Pheretima posthuma Kinberg) earthworm in respect of its impact on total protein, protein mobility by electrophoresis and activity of cholinesterase. By applying the contact cum feeding method the earthworms were exposed to the test materials. Three major parts of LD50 exposed alive and active earthworms have been subjected to the estimation of total protein amounts, the activity of cholinesterase and for protein mobility through native gel electrophoresis. The average percent mortality was found to be 20%, 40%, 60%, 70% and 90% and 20%, 30%, 40%, 60% and 80% of post treatments in respect of doses i.e. 0.06, 0.12, 0.24, 0.48, 0.96 ppm of soil, under the effect of sulfoxaflor and nitenpyram respectively. The average percent mortality was found to be 20%, 40%, 60%, 80%, 90% and 20%, 30%, 40%, 50%, 70% and 10%, 20%, 30%, 40% and 60% against the treatment doses of 0.50, 1.0, 2.0, 4.0 and 8.0 ppm in soil by the spinetoram, azoxistrobin and neem leaf extract respectively. The LD50 values of neem leaf extract were foundat 5.47 ppm as compared to the LD50 values of other four compounds under studies sulfoxaflor, nitenpyram, spinetoram, azoxystrobin were observed as 0.1841, 0.2908, 1.4288, 3.2107 ppm of soil respectively. It was observed that in the peristomium region amongst all the treatments the preponderance amount of protein was found as 56.5>38.86>35.23>30.6>28.6 mg/ml at post treatment of neem extract, nitenpyram, sulfoxaflor, spinetoram and azoxystrobin respectively. In the clitellum region amongst all the treatments the preponderance amount of protein was found at 66.8>42.0>48.1>43.2>34.0 mg/ml at post treatment of neem leaf extract, sulfoxaflor, nitenpyram, azoxystrobin and spinetoram respectively, while in the abdomen region the total amount of protein was found as 58.0>44.5>39.0>36.0>35.0 mg/ml at post treatment of neem leaf extract, spinetoram, nitenpyram, azoxystrobin and sulfoxaflor respectively. Comparatively, in the control batch the total amount of protein was found in the peristomium region as 66.1-78.2 mg/ml, clitellum region as 72.0-85.0 mg/ml and abdomen region as 60.0- 78.0 mg/ml. In the peristomium region amongst all the treatments, the cholinesterase inhibition was found at 30sec as 86%>86.00%>85.38%>81.33%>76.68% at post treatments of azoxystrobin, nitenpyram, sulfoxaflor, spinetoram, and neem extract respectively, the cholinesterase inhibition was found at 60 sec as 89.55%>88.10%> 87.22%>86.52%>72.39% at post treatments of nitenpyram, azoxystrobin, spinetoram, sulfoxaflor and neem extract respectively, the cholinesterase inhibition was found at 90sec as 95.11%>87.60%>87.39%>84.42%>79.01% at post treatments of spinetoram, nitenpyram, azoxystrobin, neem extract and sulfoxaflor respectively. In the clitellum region amongst all the treatments, the cholinesterase inhibition was found at 30sec as 57.11%>51.62%>27.09%>25.46% at post treatments of nitenpyram, spinetoram, sulfoxaflor and azoxystrobin respectively, the cholinesterase inhibition was found at 60sec as 52.00%>28.81%>19.42%>09.33% at post treatments of sulfoxaflor, spinetoram, nitenpyram and azoxystrobin respectively, the cholinesterase inhibition was found at 90sec as 68.84%>33.58%>23.44%>22.90% at post treatments of nitenpyram, sulfoxaflor, azoxystrobin and spinetoram respectively. While, in the case of treatment with neem leaf extract, a cholinesterase enhancement case was found in the clittelum region at 15.09%, 09.04% and 30.23% at the intervals of 30sec, 60 Sec and 90 Sec respectively. In the abdomen region amongst all the treatments, the cholinesterase inhibition was found at 30sec as 90.00%>81.58%>64.89%>64.89%>51.50% at post treatments of nitenpyram, sulfoxaflor, spinetoram, azoxystrobin and neem leaf extract respectively, the cholinesterase inhibition was found at 60 sec as 74.29%>73.96%>73.96%>60.59%>52.77% post treatments of spinetoram, nitenpyram, sulfoxaflor, azoxystrobin and neem leaf extract respectively, the cholinesterase inhibition was found at 90sec as 77.76%>68.84%>50.72%>34.61% >33.58% at post treatment of spinetoram, nitenpyram, azoxystrobin, neem leaf extract and sulfoxaflor respectively. In the present work, the impacts of sulfoxaflor, nitenpyram, spinetoram, azoxystrobin and Azadirachta indica (Neem) on exposure to earthworm Pheretima Posthuma Kinbergin peristomium, clitellum and abdomen regions have been determined by employing 6% native gel electrophoresis. The estimated proteins as observed in the region of peristomium of earthworm designated as proteins–Rm–0.987 and Rm–0.025 were found only in neem treated, proteins–Rm–0.900, Rm–0.600 and Rm–0.125 were newly appeared in azoxystrobin treated, proteins–Rm–0.892 and Rm– 0.383 were present in sulfoxaflor treated, newly appeared proteins–Rm–0.851, Rm–0.679 and Rm–0.283 were present in nitenpyram treated, proteins–Rm–0.567, Rm–0.370 and Rm–0.271 were found in spinetoram treated only and proteins–Rm–0.650, Rm–0.450, Rm–0.312 and Rm–0.135 were observed in control samples. Some proteins were found in contrast treatments i.e. proteins–Rm–0.925 and Rm–0.135 were present in control and neem treated, protein- Rm–0.792 has been found in control and azoxystrobin treated and a distinctive protein–Rm–0.723 has been only found in sulfoxaflor and spinetoram treated worms. In the clitellum regions, appeared proteins–Rm–0.938, Rm–0.809, Rm–0.415 and Rm–0.158 were present in sulfoxaflor treated, proteins–Rm–0.937, Rm-0.737and Rm–0.150 have been found in spinetoram treated, proteins–Rm–0.925, Rm–0.792, Rm–0.450 and Rm–0.312 were found in control, proteins–Rm–0.920, Rm–0.400 and Rm–0.162 have been observed in nitenpyram treated, proteins–Rm–0.887, Rm–0.762, Rm–0.375, Rm–0.125 and Rm–0.025 have been observed in neem treated and Protein–Rm–0.250 was present in azoxystrobin treated samples only. While, few same proteins were found in contrast treatments i.e. protein–Rm–0.600 was merely found in sulfoxaflor and nitenpyram treated, protein–Rm–0.525 was observed in azoxystrobin and neem leaf extract treated samples and proteins– Rm–0.650 and Rm– 0.135 were observed in control and azoxystrobin treated. Whereas, in the abdomen regions freshly, emerged proteins–Rm–0.975, Rm– 0.875, Rm–0.737, Rm–0.387, Rm–0.387 and Rm–0.050 were present in neem treated samples, proteins–Rm–0.925, Rm–0.792, Rm–0.650, Rm–0.450, Rm–0.312 and Rm– 0.135 were found in control treated, proteins–Rm–0.827, Rm–0.617, Rm–0.419 and Rm–0.209 were found in nitenpyram treatement, proteins–Rm–0.756, Rm–0.609, Rm–0.390 and Rm–0.219 were merely found in spinetoram treated samples, unique proteins-Rm–0.750, Rm–0.612, Rm–0.412, Rm–0.325 and Rm–0.0625 were only found in azoxystrobin treated and proteins–Rm–0.861, Rm–0.646 and Rm–0.507 have been observed in sulfoxaflor treated samples, while, all above mentioned proteins absent in contrast treatments of sulfoxaflor, nitenpyram, spinetoram, azoxystrobin, neem treated and control samples.