Gupta, Dr. Pushpraj S.ANJALI2018-04-052018-04-052018http://krishikosh.egranth.ac.in/handle/1/5810042927Increasing bacterial resistance is concomitant with the volume of antibiotic consumed, as well as missing doses when taking antibiotics. Inappropriate prescribing of antibiotics has been credited to a number of cases of drug resistance. To conquer drug resistance the discovery of new derivatives are obligatory as preexisting drugs are now less affective, most drugs existing presently at the market are varied heterocyclic compounds, amongst these compounds the five-membered heterocycles represent a broad and differentiated group with extensive range of biological activity. The current generations drugs necessitate definite variation to improve efficacy and to conquer multiple drug resistance. From literature survey it was proved that aminoquinoline, triazole and benzothiazole rings are present in antimicrobial, analgesic and anti-inflammatory agents. The presented work explores synthesis, characterization and evaluation of antimicrobial activity of new heterocyclic compounds bearing quinoline derivatives having Benzothiazole and 1,2,4 triazole nucleus. Structures were confirmed by FT-IR, 1H NMR, Elemental analysis, Mass spectral analytical studies. Method: A series of derivatives of 4-(Substituted Benzothiazol-2-ylamino)-5-[2-(7-chloro-quinolin-4-ylamino)-ethylamino] Substituted methyl-2,4-dihydro-[1,2,4] triazole-3-thione (4a-4k,5a-5k,6a-6k) were synthesized via three major step protocol. In the first major step formation of 4-Amino-5-[2-(7-chloro-quinolin-4-ylamino)-ethylamino]-4H-[1,2,4] triazole-3-thiol take place via five series of reaction where at first step 4,7-dichloroquinoline react with 1,3-diamino propane however second step involve reaction between derivative (1a) with phenyl chloroformate in presence of triethylamine leads to the formation of 1-[2-(7-chloro-quinolin-4-ylamino)-ethyl]-carbamic acid phenyl ester (1b) . Formation of N-{2-[(7-chloro quinolin-4 yl) amino] ethyl} hydrazine carboxamide (1c) achieved in third step where hydrazine monohydrate react with compound 3 using methanol as solvent further forth step involve potassium dithiocarbazinate (1d) synthesis where derivative 1c reacted with KOH and carbon disulfide using ethanol as solvent. Fifth synthetic protocol involve synthesis of 4-amino-5-[2-(7-chloro-quinolin-4-ylamino)-ethyl amino]-4H-[1,2,4]triazole-3-thiol (1e) where derivative (1d) unite with hydrazine hydrate. The second major step formation of 2-Chloro-substituted Benzothiazole (2b) via two step reaction involving the substituted aniline with ammonium thiocyanate followed by bromination in the presence of glacial acetic acid leads to formation of Substituted benzothiazol-2-yl amine (2a), Further it is reacted with sodium nitrite in the solution of phosphoric acid followed by addition of brine solution and copper sulphate solution. The third major step involve the formation of 4-(Substituted Benzothiazol-2-ylamino)5-[2-(7-chloro-quinolin-4-ylamino)-ethylamino]-2substituted methyl-2,4-dihydro-[1,2,4] triazole-3-thione(4) via formation of 4 (Substituted Benzothiazol-2-ylamino)-5-[2-(7-chloro-quinolin-4-ylamino)-ethyl amino]-4H-[1,2,4]triazole-3-thiol (3) where 2b reacts with 1e in the presence of equimolar amount of the 4-chlorobenzoyl chloride in the presence of sodium hydroxide solution. Synthesized derivatives (4a-4k, 5a-5k, 6a-6k) were evaluated for antibacterial, antifungal, anti-inflammatory and analgesic activity. Antimicrobial activity tested by agar disc diffusion method and Minimum inhibitory concentration against gram positive (Bacillus subtilis, Bacillus cereus, Staphylococcus aureus) and gram negative (Escherichia. coli, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa) and antifungal activity against Aspergillus niger, Candila albicans, Aspergillus clavatus. Synthesized derivatives 4i,4j,5a,5b,5c,5d,5e,6f,6j showed higher zone of inhibition and low MIC against given microbes compared with standard drug Ciprofloxacin and Fluconazole at different dilutions. The statistical analysis of data was done by using SPSS Trial version 20 and Microsoft Excel 2013 to correlate the MIC and Zone of Inhibition. The vivo pharmacological activity evaluation includes anti-inflammatory activity by carrageenan-induced rat paw edema method and analgesic activity by Tail flick method and hot plate method. The statistical analysis of data was done by using one-way ANOVA followed by Dunnett’s test using Graph Pad Instant software. The synthesized derivatives 4b having piperazine ring while 5k having 2-Methyl aniline nucleus and compound 5c having thiourea nucleus showed more than 50% paw edema inhibition at 100mg/Kg dose for 3 hours and 4 hours respectively compared to standard drug Meloxicam at 13.5 mg/Kg orally. Analgesic activity evaluation by tail flick model measured at 0 h, 1 h, 2 h, 3 h and 4 h for all test groups (150 mg/kg orally) compared with standard drug Diclofenac sodium by digital analgesiometer. Study showed that among all synthesized derivatives, the compounds 4e, 5e, 6e emerged as most potent analogues indicating the significant role of acetamide group in analgesic activity while synthesized compound having thioacetamide (6d) and 4-Bromo aniline (6g) in fluorine substituted benzothiazole showed improved antinociceptive activity in tail flick response. Compounds 4b, 4g, 5b, 6e, 6k exhibited significant activity by increasing the time of response of paw linking and jumping when compared with standard drug Diclofenac sodium (1mg/Kg b.wt.) in hot plate method.ennullThesis