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Synthesis and Biological Evaluation of 1, 2, 3-Benzotriazin-4 3H One Based Compounds

Thesis Info

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Author

Khalid, Zunera

Program

PhD

Institute

University of the Punjab

City

Lahore

Province

Punjab

Country

Pakistan

Thesis Completing Year

2019

Thesis Completion Status

Completed

Subject

Chemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/10650/1/Zunera%20Khalid.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727434214

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This dissertation; Synthesis and biological evaluation of 1,2,3-benzotriazin 4(3H)-one based compounds comprises easy preparation of new compounds and study of their enzyme inhibition assay. Three series of 1,2,3-benzotriazin-4(3H)-one sulfonamide / carboxamides were synthesized in good to excellent yields. For the preparation of first series isatin was converted to isatoic anhydride, then reacted with sulfanilic acid followed bydiazotization to cyclize to 4-(4-oxobenzo[d][1,2,3]triazin 4(3H)-yl)benzenesulfonic acid. The acid was directly converted to series of sulfonamides by using 1,3,5-trichlorotriazine:N,N-dimethylformamide (TCT: DMF) adduct at room temperature. The reaction was found successful only for electron rich anilines. For the second series, isatin was converted to of 4-(4 oxobenzo[d][1,2,3]triazin-3(4H)-yl)butanoic acid through isatoic anhydride. Then N (4-(1H-benzotriazol-1-yl)-4-oxobutyl)benzo[1,2,3]triazin-4(3H)-one was synthesized by reacting the acid with thionyl chloride and benzotriazole. Further at room temperature benzotriazole moiety was replaced with different amines and anilines to afford amide derivatives. In another series 6-amino-N-alkyl-1,2,3-benzotriazin-4(3H)-ones were used to prepare sulfonamide derivatives by reaction with different sulfonyl chlorides. All the prepared compounds were evaluated for their enzyme inhibition potency. α-Glucosidase, Urease and Acetylcholinesterase were used to study. Results indicated that most of the compounds have potential to inhibit α-glucosidase better as compared to standard drugs. Anti-urease results showed fair to good inhibition activity but less than refernce compound; thiourea. In case of acetylcholinesterase, none of the compound found active.
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محمد مجید زبیری

محمد مجید زبیری
افسوس ۲۳؍ مئی کو شبلی کالج کے سابق استاد جناب محمد مجید زبیری کا علی گڑھ میں انتقال ہوگیا، ریٹائر ہونے کے بعد وہ جناب سید صباح الدین عبدالرحمن مرحوم کے اصرار پر دارالمصنفین کے شعبۂ انصرام سے وابستہ ہوئے، اپنی نیکی، بھلمنساہت، صلح پسند طبیعت اور ایمانداری و دینداری کی وجہ سے ہر طبقہ میں مقبول و محترم تھے، صحافی و شاعر بھی تھے تقریباً دو سال قبل سخت بیمار ہوئے، علاج کے لیے اپنی صاحبزادی کے پاس علی گڑھ چلے گئے اور وہیں سے سفر آخرت اختیار کیا، اﷲ تعالیٰ بال بال مغفرت فرمائے اور پس ماندگان کو صبر و رضا کی توفیق دے، آمین۔ (ضیاء الدین اصلاحی، جون ۱۹۹۲ء)

نقد المتن عند المحدثين بين القبول والرد

تهدف هذه الدراسة للرجوع إلى موضوع نقد المتن عند المحدثين للكشف عن جهودهم في الدفاع عن السنّة النبوية الشريفة عن طريق نقد ما لا يصح من المتون، فموضوع الدراسة بقدر ما هو واضح المعالم وبيّن إلا أن الخطأ فيه لا يُغتَفر كون أنَّه يتعلق بحفظ السنّة، ولقد اعتمد الباحث على المنهج الوصفي التحليلي القائم على سرد وتحليل الأحاديث المتعلقة بالموضوع، وتوصل الى عدّة نتائج أهمها أن: المحدث في حالة النقد ينظر الى السند والمتن معاً على حد سواء، وأن جهود العلماء المتقدمين في نقد المتون متنوعة بحسب الفن التحديثي، وقد أوصى الباحث بضرورة تجميع وترتيب جهود العلماء المتقدمين والمتأخرين حسب التخصص لحل إشكالية نقد المتون عند المحدثين. الكلمات المفتاحية: نقد المتن، المحدثون، السنة النبوية، السيرة النبوية، الحديث الشريف.

Producation and Characterization of Colored Metabiolites and Pigments of Microbial Isolates

Among different microbes, fungi have been found as an important source of various exogenous natural color metabolites and pigments of immense industrial importance in sectors of food, dyeing, pharmaceutical and cosmetic. Based upon these facts, the present study evaluated the potential of selected fungal isolates towards production of color metabolites. Besides, the color metabolites were biochemically characterized in addition to their biological activities. Colored secondary metabolites production and their bioactive potential were evaluated in three different newly isolated fungi. Two of these fungi were isolated from Kala pani soil and identified as Penicillium verruculosum SG (KC698959) and Aspergillus fumigatus SG4 (JX863917) whereas, the endophytic fungus isolated from Taxus baccata was Chaetomium strumarium. The pigment production was initially screened out on solid state fermentation conditions using five different media however, Potato dextrose agar (PDA) proved to be the best culture medium. In liquid state fermentation conditions, Potato dextrose broth (PDB) was selected as the best culture medium. After selection of the culture media, different operational parameters viz, pH, temperature, carbon source and concentration, nitrogen source and C: N ratios were optimized. Overall, the production was most efficient at pH 5.5, with 20-40g/L glucose (C source) and yeast extract (N source), C: N ratio was 4:1 for Penicillium verruculosum; 10:1 for Chaetomium strumarium and 8:1 for Aspergillus fumigatus under mesophilic temperature (25-30˚C) in PDB. Standard qualitative and quantitative screening test of the colored extracts of fungi indicated presence of important classes of compounds viz. phenols, flavonoids, anthraquinones, terpenoids, alkaloids and coumarins, showing some similarity between plant and fungal pigments whereas, tannins were absent in them. These compounds were considerably stable in a pH range of 5-8 and ≤100˚C with red pigment of Penicillium verruculosum being stable at even acidic conditions i.e., pH 3.Pigmented filtrates of the fungi revealed a significant antimicrobial activity in terms of zone of inhibition (mm) against test pathogenic bacteria (0-24) and fungi (0-30). Besides, they showed varying antioxidant (EC50 = 7-21 µg/mL) and free radical scavenging activities [EC50 (DPPH) = 10-38, (ABTS) = 95-134 µg/mL]. Howover, the pigmented filtrates of fungi showed a low level of phytotoxicity (Seed germination and shoot length) and cytotoxicity (EC50). Such potential characteristics indicated the likelihood of their utilization in food and pharmaceutical industries. Fungal isolates viz. Penicillium verruculosum SG, Aspergillus fumigatus SG4 and Chaetomium strumarium SG1 were evaluated for the production of bioactive color metabolites on optimized potato dextrose broth (25˚C). Logical fragmentation pattern following column chromatography, thin layer chromatography (TLC) and liquid chromatography and mass spectrometry (LCMS) of crude culture filtrate of fungus Penicillium verruculosum SG demonstrated presence of polyketide pigments (Monascorubrin, Monascin, Glutamyl Monascorubrine and analogue of Monascorubrine) and other different bioactive compounds viz. Pyripyropene, Orevactaene, N-De methyl Calcimycin and Citrinadin.Cytotoxicity against five different cell lines i.e., KA3IT, MDCK, HSCT6, NIH3T3 and HEK293 of the selected colored fractions of fungal filtrate containing different compounds revealed IC50 (µg/mL) values ranging from 5-100. It was comparatively higher in case of Orevactaene (5+0.44) [(non-significantly differed with Monascorubrine)] followed by Pyripyropene (8+0.63) against cancer cell line KA3IT. Overall, these compounds significantly showed less toxicity towards normal cell lines. X ray crystallography of yellow crystals of a pure compound (224.21 m/z) confirmed its 3 dimensional structure and was identified as Phenazine 1 carboxylic acid (C13H8N2O2), which is previously known as a broad spectrum antibiotic, antifungal and bio-control agent. Some unknown compounds not found in libraries were also detected in the culture filtrate. In case of Chaetomium strumarium, logical fragmentation pattern following column chromatography, TLC and LCMS of crude culture filtrate revealed the presence of colored compounds i.e., Monascorubramine (purple red), Alizarin and Cochliodinol (Purple). Besides, bioactive colorless compounds Dihydromaltophytin, Nivalenol and Paxilline were also detected. Overall, cytotoxicity against all five cell lines i.e., KA3IT, MDCK, HSCT6, NIH3T3 and HEK293 of the selected colored fractions of fungal filtrate containing different compounds revealed IC50 (µg/mL) values ranging from 1-73 µg/mL. It was comparatively higher in case of Nivalenol/Paxilline (10.6±9.76) followed by crude filtrate (28± 20.4) [(Non-significantly differed with Cochliodinol, Monascorubramine and Alizarin)] > Dihydromaltopytin (45.2±24.4). Overall, these compounds significantly showed less toxicity towards normal cell lines. Whereas in case of cancer cell line KA3IT, Cochliodinol containing fraction was most effective (1IC50=0±0.44) [(Non significantly differed from crude culture filtrate)] followed by Nivalenol/Paxilline containing fraction (20±0.34) [(Non significantly different from Dihydromaltophytin and Alizarin)] >Monascorubramine (50±0.89). A pure orange compound was isolated and its proton NMR and LCMS confirmed it to be anthraquinone compound. Besides, many unknown compounds were also detected in LCMS profile of the selected fungi. In Aspergillus fumigatus, logical fragmentation pattern following column chromatography, TLC and LCMS of crude culture filtrate revealed the presence of colored compounds i.e., PPR Monascorubramine and Fusarubin. Other colorless bioactive compounds were also detected in the fungal filtrate i.e., Pyrrocidine b, Communosine g, Teritrem and Tryptoquialanine A and B. Overall, the cytotoxicity against the five cell lines viz. KA3IT, MDCK, HSCT6, NIH3T3 and HEK293 shown by these compounds ranged from 1-200 µg/ml. All the fractions of this fungus showed quite low cytotoxicity (IC50) value i.e., 1-1.5 µg/ml against cancer cell line (KA3IT) which differed significantly from crude culture filtrate (2.8±0.44). Overall, the pigmented filtrate of this fungus was more cytotoxic as compared to the other 2 fungi showing its higher anticancer potential. Fungi proved to be an important source of colored metabolites of polyketide nature. Production of these metabolites helped under mesophilic temperature, pH (5.5-7), glucose and yeast extract. Stability of the metabolites was considerably high at temperature < 100˚C though it varied a little with varying pH clearly predicting their industrial applications. Furthermore, detailed evaluation of different compounds in various fractions of fungal filtrates typically indicated their non-toxic nature and role as biomedical agent in treating cancer. The study concludes that optimized yield of aforementioned compounds by manipulating different biotechnological procedures can further help their large scale application in pharmaceutical, cosmetic and food industries. However, large scale production and application is still needed to be explored.