Design and Screening of PPAR-γ agonist based Isatin derivatives and its remarkable activity as Anti-cancer and Anti-diabetic
Y. B. Zambare*, S. S. Chitlange, R. P. Bhole
Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri.
*Corresponding Author E-mail: zambare007@gmail.com
ABSTRACT:
Isatin are flexible compound, where it can be used for the preparation of a large number of substituted heterocyclic compounds, such as pyrazole, benzofuran, pyridazinone and sulphonamides. Sulphonamides is important class such as carbonic anhydrase inhibitors, antibacterial, antitumor, diuretic, hypo-glycemic, antidiabetic and anti-thyroid. In the past few decades, research has reached to the mark with an increased interest in capturing novel methodologies and targets that forcefully worked for the preparation isatin based sulphonamides derivatives. This review covers updated information of most of the active isatin based sulphonamides derivatives that have been shown considerable novel synthetic schemes as well as pharmacological and biological actions by targeting them on PPAR-γ agonist. From these considerations, ideas for future molecular modifications by different synthetic scheme leading to preparation of compounds with greater favorable pharmacological and biological properties may be derived.
KEYWORDS: Isatin based sulphonamides, PPAR-γ, antitumor, antidiabetic.
INTRODUCTION:
A number of sulfonamides and their derived compounds have been reported for their antibacterial (1), antitumor (2), anti-carbonic anhydrase (3), diuretic, hypoglycaemic (4), antithyroid and protease inhibitory activity (5). Due to their significant pharmacology applications and wide- spread use in medicine, these compounds have gained attention in bio-inorganic and drug chemistry. In this context, some now Isatin based sulfonamides their derivatives have been reported with their potential antidiabetic and anticancer agents against various bacterial and fungal resistant species, whose increasing incidence is emerging globally as a major problem in drug therapy.
1. Severe Acute Respiratory Syndrome:
Wei Liu et al (6) were synthesized a series of isatin derivatives as possible SARS-CoV 3CLpro inhibitors was designed, synthesized, and evaluated by in vitro protease assay using fluorogenic substrate peptide, in which several showed potent inhibition against the 3CLpro. Structure–activity relationship was analyzed, and possible binding interaction modes were proposed by molecular docking studies. Among all compounds, 8k1 showed most potent inhibitory activity against 3CLpro (IC50 = 1.04 µM). These results indicated that these inhibitors could be potentially developed into anti-SARS drugs.
2. Antitumor activity:
Hatem A. Abdel-Aziz et al (7) prepared a new series of benzenesulfonamide derivatives incorporating pyrazole and isatin moieties. Biological evaluation of the target compounds was performed against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and more precisely against the human isoforms hCA I, II (cytosolic), IX and XII (transmembrane, tumor-associated enzymes). Most of the tested compounds efficiently inhibited hCA I, II and IX, with KIs of 2.5- 102 nM, being more effective than the reference drug acetazolamide. Compounds 11e, 11f, 16e and 16f were found to inhibit hCA XII with Ki of 3.7, 6.5, 5.4 and 7.2 nM, respectively. Compounds 11e and 16e, with 5-NO2 substitution on the isatin ring, were found to be selective inhibitors of hCA IX and hCA XII. Docking studies revealed that the NO2 group of both compounds participate in interactions with Asp132 within the hCA IX active site, and with residues Lys67 and Asp130 in hCA XII, respectively.
3. Anticancer activity:
Piyush Trivedi et al (8) synthesized a novel series of 3-(2-oxo-2-phenylethylidene)indolin-2-ones incorporating pharmacophoric elements of isatins and chalcones were designed and synthesized. The compounds were evaluated for anticancer activity against three breast cancer cell lines. Most of the compounds showed promising anticancer activity (< 20 nM) against the studied cell lines. Compound 2c, bearing a 5-chloro substituent in the benzo ring of the isatin moiety and 3,4-dimethoxy substitutions in the phenyl ring, was found to be the most active in the series with GI50 values of 8.54, 4.76 and 3.59 against MDA-MB231, MDA-MB468 and MCF7 cells, respectively. Overall, the findings of the study highlight 3-(2-oxo-2-phenylethylidene) indolin-2-one as a potential new lead in the search of drugs for the treatment of breast cancer.
4. Antitumor activity:
Wagdy M. Eldehna et al (9) synthesized Three series of indolinone-based sulfonamides (3a-f, 6a-f and 9a-f) were in vitro evaluated as inhibitors of the tumor-associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA IX and XII, using a stopped-flow CO2 hydrase assay. All the investigated sulfonamides displayed single- or double-digit nanomolar inhibitory activities towards both hCA IX (KIs: 6.2 – 64.8 nM) and XII (KIs: 7.1 – 55.6 nM) isoforms. All sulfonamides (3a-f, 6a-f and 9a-f) were in vitro examined for their potential anticancer activity against colorectal cancer HCT- 116 and breast cancer MCF-7 cell lines. Sulfonamide 9e was found to be the most potent counterpart against HCT-116 (IC50 = 3.67 ± 0.33 µM). Sulfonamide 9e displayed good selectivity profile for inhibition of the tumor-associated isoforms (CAs IX & XII) over the off-target cytosolic CAs I and II. 9e was screened for cell cycle disturbance and apoptosis induction in HCT-116 cells.
5. Anti mycobacterial activity:
Guangming Lu et al (10) reported the design and synthesis of a series of novel benzofuran-isatin hybrids, and in vitro evaluation of their anti-mycobacterial activity against both drug-susceptible and multi-drug resistant (MDR) Mycobacterium tuberculosis (MTB) strains. In parallel, cytotoxicity of these hybrids was also tested in VERO cells. Preliminary results indicated that all hybrids with acceptable cytotoxicity in VERO cells (CC50: 128->1,024 µg/mL) exhibited considerable anti-mycobacterial activities against MTB H37Rv and MDR-TB with MIC ranging from 0.25 to 8 µg/mL. It is worth noting that hybrid 8f with no cytotoxicity towards VERO cells (CC50: >1,024 µg/mL) was found to be the most active compound (MIC: 0.25 and 0.5 µg/mL) against MTB H37Rv and MDR-TB strains.
6. Anticancer drug:
Hany S. Ibrahim et al(11) synthesized and characterised of two new sets of arylsulfonehydrazone benzenesulfonamides (4a-4i with phenyl tail and 4j-4q with tolyl tail) are reported. The compounds were designed according to a dual-tails approach to modulate the interactions of the ligands portions at the outer rim of both hydrophobic and hydrophilic active site halves of human isoforms of carbonic anhydrase (CA, EC 4.2.1.1). The synthesized sulfonamides were evaluated in vitro for their inhibitory activity against the following human (h) isoforms, hCA I, II, IV and IX. With this latter being a validated anticancer drug target and marker of tumor hypoxia, attractive results arose from the compounds inhibitory screening in terms of potency and selectivity.
7. Anticancer drug:
Wagdy M. Eldehna et al(12) herein we reported the synthesis and biological evaluation of novel sulfonamides (5a-h, 10a-g and 11a-c) incorporating substituted 2-indolinone moiety (as tail) linked to benzenesulfonamide (as zinc anchoring moiety) through a hydrazide linker. The synthesized sulfonamides were evaluated in vitro for their inhibitory activity against the following human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII. All these isoforms were inhibited by the sulfonamides reported here in variable degrees. hCA I was inhibited with KIs in the range of 671.8: 3549.5 nM, hCA II in the range of 36.8: 892.4 nM; hCA IX in the range of 8.9: 264.5 nM, whereas hCA XII in the range of 9.0: 78.1 nM. In particular, compound 10b emerged as a single-digit nanomolar hCA IX and XII inhibitor (8.9 and 9.2 nM, respectively). Molecular docking studies were carried out for compound 10b within the hCA II, IX and XII active sites, allowed us to rationalize the obtained inhibition results.
8. Antidiabetic activity:
Fazal Rahim et al(13) were carried out worked on isatin base Schiff bases (1-20) were synthesized, characterized by 1HNMR and EI/MS and evaluated for α-glucosidase inhibitory potential. Out of these twenty (20) compounds only six analogs showed potent α-glucosidase inhibitory potential with IC50 value ranging in between 2.2 ± 0.25 to 83.5 ± 1.0µM when compared with the standard acarbose (IC50 = 840±1.73 µM). Among the series compound 2 having IC50 value (18.3 ± 0.56 µM), 9 (83.5 ± 1.0 µM), 11 (3.3 ± 0.25 µM), 12 (2.2 ± 0.25 µM), 14 (11.8 ± 0.15 µM), and 20 (3.0 ± 0.15µM) showed excellent inhibitory potential many fold better than the standard acarbose. The binding interactions of these active analogs were confirmed through molecular docking.
9. Anticancer activity:
Qizheng Yao et al(14) carried out worked on eighteen symmetrical bis-Schiff base derivatives of isatin were synthesized by condensation of the natural or synthetic isatins with hydrazine and were evaluated for their in vitro and in vivo antitumor activities. More than half of the obtained compounds showed potent cytotoxicity according to the MTT assay on five different human cancer cell lines (i.e. HeLa, SGC-7901, HepG2, U251, and A549), with compound 3b 3,30-(hydrazine-1,2-diylidene)bis (5-methylindolin-2-one) being the most potent com- pound on HepG2 (IC50 w 4.23 mM). 3b was also found to be able to inhibit substantially the tumor growth on the HepS-bearing mice at a dose of 40 mg/kg. The real-time live cell imaging and tracking in the H2B- labeled HeLa cells revealed that 3b could induce mitosis interference and apoptosis-associated cell death. In mechanism study, 3b arrested the cell cycle at the G2/M phase in HepG2 cells by down-regulating the expression of cyclin B1 and cdc 2.
10. Antidiabetic activity:
Mohammad Sarwar Alam et al (15) were synthesized Twenty one pyrazoline containing benzenesulfonylureas and docked against PPAR-γ target. All the compounds were first screened for their antidiabetic potential by oral glucose tolerance test and then six active compounds were assessed on STZ diabetic model. It was found that five compounds showed significantly high antidiabetic activity in comparison to glibenclamide as well as rosiglitazone (standard drugs). The active compounds were evaluated for their effect on body weight since weight management is one of the main concerns associated with sulfonylureas. Finally, the most active compound 6f was shown to elevate PPAR-γ gene expression. The synthesized compounds were also screened for anticancer activity by National Cancer Institute. Five compounds (5i, 6e, 6g, 6i and 6j) were selected at one dose level and showed potency against cancers.
11. Antidiabetic activity:
Kalim Javed et al (16) synthesized thirty new aryl-pyridazinone-substituted benzenesulphonylurea derivatives (I–XXX) and evaluated for their anti-hyperglycaemic activity in glucose-fed hyperglycaemic normal rats. Twenty-three compounds (III–XI, XIV–XVII, XIX–XXIV, XXVI and XXVIII–XXX) showed more or comparable area under the curve (AUC) reduction percentage (ranging from 21.9% to 35.5%) as compared to the standard drug gliclazide (22.0%). On the basis of docking results, 18 compounds were screened for their in vitro ability to inhibit rat lens aldose reductase. Ten compounds (III–VI, XII, XVI–XVIII, XXI and XXVII) showed ARI activity with IC50 ranging from 34 to 242 mM.
12. Antibacterial activity:
Zahid H. Chohan et al (17) reported Pyrrolyl and thienyl derived sulfonamides and their metal [cobalt(II), copper(II), nickel(II) and zinc(II)] complexes were synthesized and characterized by elemental analyses, molar conductances, magnetic moments, IR, 1HNMR, 13C NMR and electronic spectral data. These compounds were screened for in-vitro antibacterial activity against four Gram-negative (Escherichia and two Gram-positive The results of these studies revealed that all compounds showed significant to moderate antibacterial activity; however, the zinc complexes were shown to be the most active against various species.
13. Antibacterial activity:
Hazoor a. Shad et al (18) investigated 2-Hydroxy-1-naphthaldehyde derived sulfonamides and their first row d-transition metal chelates [cobalt (II), copper (II), nickel (II) and zinc (II)] have been synthesized and characterized. The nature of bonding and structure of all the compounds have been deduced from elemental analyses, infrared, 1H NMR, 13C NMR, mass spectrometry, electronic spectra, magnetic susceptibility and conductivity measurements. An octahedral geometry has been suggested for all the complexes.
14. Antitumor activity:
Yuou Teng et al (19) designed and synthesized forty four di- or trisubstituted novel isatin derivatives. Their structures were confirmed by 1H NMR and 13C NMR as well as LC–MS. The anticancer activity of these new isatin derivatives against three human tumor cell lines, K562, HepG2 and HT-29, were evaluated by MTT assay in vitro. SAR studies suggested that the combination of 1-benzyl and 5-[trans-2-(methoxycarbonyl) ethen-1-yl] substitution greatly enhance their cytotoxic activity, whereas an intact carbonyl functionality on C-3 as present in the parent ring is required to such a potency. This study leads to the identification of two highly active molecules, compounds 2h (IC50 = 3 nM) and 2k (IC50 = 6 nM), against human leukemia K562 cells.
15. Anticancer activity:
Claudiu T. Supuran et al (20) newly prepared a series of Schiff’s bases 3-formyl-chromone or 6-methyl-3-formyl-chromone with aromatic sulfonamides, such as sulfanilamide, homosulfanilamide, 4-aminoethyl-benzenesulfonamide, a pyrimidinyl-substituted sulfanil- amide derivative, sulfaguanidine and 4-amino-6-trifluoromethyl-benzene-1,3-disulfonamide. The zinc complexes of these sulfon- amides have also been obtained. The new derivatives and their Zn(II) complexes were investigated for the inhibition of four phys- iologically relevant isozymes of carbonic anhydrase (CA, EC 4.2.1.1): the cytosolic isoforms I and II, as well as the tumor-associ- ated, transmembrane isozymes CA IX and XII. Except for the sulfaguanidine-derived compounds which were devoid of activity against all isozymes, the other sulfonamides and their metal complexes showed interesting inhibitory activity.
16. Antitumor activity:
Mahmood- Ul-Hassan, Zahid H. Chohan, Andrea Scozzafava & Claudiu T. Supuran (21) discovered Schiff’s bases from aromatic/heterocyclic sulfonamides and amino-sulfonamide derivatives, such as sulfanilamide, homosulfanilamide, 4-aminoethyl- benzenesulfonamide and 5-amino-1,3,4-thiadiazole-2-sulfonamide. Metal complexes of some of these Schiff’s bases, incorporating Zn(II), Co(II), Ni(II) and Cu(II) ions, were also prepared and tested as inhibitors of the zinc enzyme carbonic anhydrase (CA), and more specifically the red blood cell isozymes I and II. The Schiff’s bases behaved as medium potency CA I and CA II inhibitors, whereas their metal complexes showed a highly enhanced potency, with several low nanomolar CA II inhibitors detected.
17. Antidiabetic activity:
Joseph Vamecq (22) and co worker reported a series of eight sulfonylureas, using transfection experiments with 293T cells,and rosiglitazone as a reference PPAR-γ agonist. In the same time, results from these in vitro experiments are compared to those generated by a sound in silico PPAR-γ ligand docking procedure combined to a simple and astute strategy analysis. The latter consists of building up a dendro- gram (decision tree-like diagram) by applying three successive criteria, namely stability, conformational shape and H-binding strength of the docked sulfonylurea or rosiglitazone. This original dendrogram approach avers to be a successful way to account for our biochemical data. It discriminates also various PPAR-γ binding patterns from our small series of compounds. The recognition of these patterns is extremely im- portant because of the extraordinary potentialities of PPAR-γ ligands as therapeutic agents in diabetes, cancer, cardiovascular and neurological disorders.
18. Antidiabetic activity:
Ryu Nagata et al(23) developed a methodology based on starting with a subtle blood glucose-lowering effect of a TGF-b inhibitor, we designed and synthesized a series of benzoylpyrrole-based carboxylic acids as PPARs activators. Among these compounds, 10sNa exhibited favorable blood glucose-lowering effect without body weight gain. We assume that the bene- ficial effect of 10sNa is attributed to not only its compound PPAR agonistic activity but also its PPARγ partial agonistic activity.
19. Antidiabetic activity:
Khaled M. Darwish (24) and coworkers recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome prolif- erator activated receptor-c (PPAR-γ) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures. To further investigate this concept, two new scaffolds, the benzhydrol- and indole-based chemotypes, were introduced here in. Our optimization campaign resulted in three compounds; 15a, 15c, and 15d, with affinities in the low micromolar range on both targets.
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20. Anti-TB activity:
Tarek Aboul-Fadl et al (25) the current work involved design and synthesis of Schiff bases of nalidixic acid carbohydrazide and isatin derivatives (5,6aef and 7,8aec). Structures of the synthesized derivatives were confirmed on the bases of spectral methods of analyses. Anti-TB activity of the synthesized derivatives was investigated against four Mycobacterium strains: Mycobacterium intercellulari, Mycobacterium xenopi, Mycobacterium cheleneo and Mycobacterium smeg- matis. Modest anti-TB activity was observed within the investigated compounds, however, compound 5f revealed potent anti-TB activity with MIC 0.625 mg/ml, which is 20 times greater than the reference drug isoniazid, INH, (MIC ¼ 12.5 mg/ml). A hypothetical pharmacophore model was built using Molecular Operating Environment (MOE) program and 10 compounds structurally related to the synthesized ones with reported anti-TB activity.
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21. Analgesic activity:
R. P. Chinnasamy et al (26) synthesized a series of novel Schiff bases of isatin [5a-5l] by condensation of imesatin with different aromatic aldehydes. The imesatins were synthesized by the reaction of isatin with p-phenylenediamine. The chemical structures of the synthesized compounds were confirmed by means of Infrared (IR), Mass spectroscopy, and Elemental analysis. These compounds were screened for the analgesic activity by the tail-immersion method at a dose of 200 mg/kg body weight. Among the tested compounds 3-(4-(4-hydroxy-3-methoxylbenzylideneamino) phenylimino) indoline-2-one (5i) exhibited better analgesic activity when compared to standard pentazocine. From the above-mentioned results it may be concluded that compounds containing electron-donating groups exhibit better analgesic activity than the electron-withdrawing groups.
22. Anti TB activity:
Zao-Sheng Lv et al(27) develop novel anti-TB drugs led to the identification of several isatin-based antimycobacterial agents, among which a number of potential candidates displayed excellent antimycobacterial activity and were found to be free of cytotoxicity. This review outlines the advances in the application of isatin hybrids as antimycobacterial agents and the critical aspects of design and structure–activity relationship of these derivatives.
23. Anti-inflammatory and Antipyretic activity:
Atmakuru Ramesh and Seshaiah Krishnan S. (28) prepared schiff bases and phenyl hydrazone of isatins by reacting isatin and the appropriate aromatic primary amine/hydrazines. A new series of the corresponding N-mannich bases were synthesized by reacting them with formaldehyde and diphenylamine. The chemical structures were confirmed by means of their 1H- NMR, IR spectral data and elemental analysis. The compounds were screened for analgesic, antiinflammatory and antipyretic activity. 1-Diphenylaminomethyl-3-(1-naphthylimino)-1,3-dihydroindol-3-one (4), 3-(1-naph- thylimino)-5-bromo-1,3-dihydroindol-2-one (2) and 1-diphenylaminomethyl-3-(4-methylphenylimino)-1,3-dihy- droindol-3-one (7) were found to exhibit the highest analgesic, anti-inflammatory and antipyretic activity respectively. 1-Diphenylaminomethyl-3-(4-methylphenylimino)-1,3-dihydroindol-3-one (7) was found to be the most ac- tive compound of the series.
24. Antidiabetic acivity:
Olcay Bekircan(29) and Hakan Bektas synthesized ethyl imidate hydrochlorides 1 were prepared by passing HCl gas through solutions of substituted benzyl cyanides and absolute ethanol. Ethoxycarbonylhydrazones 2 were synthesized from the reaction of compounds 1 with ethyl carbazate. Treatment of 2 with hydrazine hydrate leads to the formation of substituted 4-amino-4,5-dihydro-1H- 1,2,4-triazole-5-ones 3. Isatin and 5-chloroisatin were added to 3 to form Schiff bases 4 and N-Mannich bases 5 of these compounds were synthesized by reacting with formaldehyde and piperidine. Their chemical structures were confirmed by means of IR, 1H- and 13C-NMR data and by elemental analysis.
25. Antidiabetic activity:
Mohammad Sarwar Alam and coworker (30) synthesized a library of twenty six benzenesulfonylureas containing thiophenylpyrazoline moiety. All the compounds were docked against PPAR-γ target. Most of the compounds displayed higher dock score than standard drugs, glibenclamide and rosiglitazone. All the synthesized compounds were primarily evaluated for their antidiabetic effect by oral glucose tolerance test. Further assessment of antidiabetic potential of sixteen active compounds was then done on STZ induced diabetic model. The results of in vivo activity by both the methods were found to be consistent with each other as well as with docking studies. Change in body weight of STZ induced animals post treatment was also assessed at the end of study. Furthermore, the compounds were screened by National Cancer Institute, Bethesda for anticancer effect and two compounds 3h and 3i were selected at one dose level since they exhibited sensitivity towards tumor cell lines (mainly melanoma).
26. Antidiabetic activity:
Pattan Shashikant R et (31) synthesised A new series of thiazolidinedione derivatives were by reacting under microwave irradiation. The structures of these compounds were established by means of IR, 1H-NMR and elemental analysis. All the compounds (B1-B9) were screened for antidiabetic activity on albino rats. Most of these compounds have shown significant antidiabetic activity when compared with the standard drug glibenclamide.
27. Antitumor activity:
Karam A. El-Sharkawy et al(32) prepared 2-cyanomethyl-thiazole-4-one (1) was obtained via the reaction of malononitrile with thioglycolic acid, then the formed product was directed toward the reaction with either acetoacetanlide or 4- chloro acetoacetanlide to produce compounds 2, 3. The latter compounds were reacted with either aromatic aldehyde or diazonium chloride derivatives to produce compounds 10, 11, 16-21 and 28-33. Finally compound 14 and 15 were obtained through the reaction of compound 10 with either malononitrile or ethylcyanoacetate. The newly synthesized compounds were evaluated for antitumor activity.
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28. Antidiabetic and Antitubercular activity:
Varsha A. Dighe(33), Rohini R. Pujar were synthesized a novel series of some substituted thiadiazole derivatives by known standard methods using analytical grade chemicals with the aim to get better antidiabetic and antitubercular activity. The structures of synthesized compounds were supported by means of physicochemical test and IR spectroscopy.
29. Antidiabetic activity
Bony R. Shah(34), Dhrubo Jyoti Sen, Rajesh Bahekar designed new series of dipeptide based DPP-IV inhibitors, which mainly consist of five membere proline ring system, attached to sterically hindered aromatic acid, with suitable linker. Total 24 new compounds were prepared, using solid phase peptide synthesis (SPPS) approach and purified by prep-HPLC. All the test compounds were subjected for DPP IV inhibitory activity and also selectivity of test compounds was assessed against DPP8, DPP9 and QPP enzymes (in vitro). Most potent compounds from each series were subjected for in vivo antidiabetic activity. In vitro, compound IIIb and IIId was found to be most active (IC50 similar to sitagliptin) and selective.
30. Antitumor activity:
K.L. Dhare et al(35) discover combretastatin, a potent anticancer molecule. It was first isolated from plant. In this continuation a series of combretastatin analogues has been synthesized on the basis of our butterfly model with two wings as aryl groups and connecting carbon chain as the body. In present study we have synthesized combretastatin analogues of different substitutions, showed potent anticancer activity against different cell lines in different fashion according to substitution. Compound 6 showed marked anticancer activity against colo-205 cell lines.
31. Antidiabetic Activity:
S.A. More(36), N.M. Bhatia synthesized a series of substituted oxazine and thiazine combinatorially and intermediate compounds were confirmed from the results of chromatographic, spectral and physicochemical analysis. By comparing the interactions of the reference and synthesized molecules with selected target enzymes DPP-4 and glucokinase enzyme, it is clear that the compound can bind strongly with the receptor molecules which suggest that rationale used to optimize structural requirements of ligand with respect to selected targets was appropriate. Two molecules 4-(4-aminophenyl)-6-(2-chloroquinolin-3-yl)-N-pyridin-2-yl-6H-1,3- oxazin-2-amine (A6B3) and 4-(2,4-dimethyl-1H-pyrrol-3-yl)-6-(2,4-dimethoxyphenyl)-N-(pyridin-2-yl)-6H-1,3- oxazin-2-amine-2-carboxylate (A4B3) showed good antidiabetic activity.
32. Antidiabetic Activity:
D. Ravi Kumar et al(37) describes the synthesis, characterization of five newly synthesized Spiro-compounds characterized by means of chromatography, IR,1H-NMR and Mass spectral analysis. The author carried in vitro anti diabetic methods like alpha amylase and alpha glucosidase methods for anti diabetic activity of tilted compounds. The investigation of anti diabetic activity revealed that the test compounds of Spiro compounds showed favorable anti diabetic activity. Among the titled compounds some were having potent antidiabetic activity.
33. Antidiabetic Activity:
Shital N. Chaskar(38), Dr. Sanjay J. Kshirsagar in their present work shows the rational design of some novel PPAR-γ agonists involving computational study performed by Molecular Design Suite (MDS) in to ligand binding domain of PPAR-γ receptor to explore conformations of molecules. The compounds synthesized using multi-step synthesis protocol. The purity of synthesized compound was ascertained by IR, NMR, Mass and elemental analysis and tested by oral glucose tolerance test (OGTT). Two molecules showed most prominent activity on hyperglycemic control.
34. Antidiabetic Activity:
Shashikant R Pattan et al(39) synthesized a new series of benzopyrone derivatives and the structure of these compounds was established on the basis of spectral data. The title compounds were evaluated for antidiabetic activity. Some of these compounds have shown excellent antidiabetic activity.
35. Anticancer Activity:
Ritesh P. Bhole(40) , Y. B. Zambare1, C. G. Bonde designed molecules were prepared following a four step reaction protocol and charac- terized on the basis of proton NMR and Mass spectrometry. These were subjected to in vitro studies by means of Oncotest and CCK-8 assays with two cell lines DU145 and 22Rv1. The selected molecules 6b and 6i were subjected to molecular docking and then for SPR based affinity assay. Results: Compounds 6b and 6i were found to be highly active anticancer compounds comparable to standard drug enzalutamide. They have significant IC50 and high dock score for the Hsp70 and Hsp90.These compounds are selective and have good binding affinity for the Hsp70 due to high Kd.
CONCLUSION:
The present review said that Isatin based sulphonamides derivatives has broad spectrum of pharmacological activity towards cancer and diabetes. From this point of view, Isatin based sulphonamide derivatives appear to be interesting. Despite their diverse therapeutic utility, there are no drugs from the sulphonamide class approved for anti-tumour therapy. Moreover, various Isatin based sulphonamide derivatives with potent anti-cancer activity are currently in either the preclinical or clinical stages. When compounds from these series can establish clinical activity to improve the quality of life, it will certainly open a new and hopeful therapeutic window for cancer as well as diabetes patients and their families.
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Received on 26.10.2018 Modified on 28.11.2018
Accepted on 31.12.2018 © RJPT All right reserved
Research J. Pharm. and Tech. 2019; 12(4):2017-2026.
DOI: 10.5958/0974-360X.2019.00335.4