Research project
IsatIn DerIvatIves wIth several BIologIcal actIvItIes
affIlIatIon:Sonam Mishra
Dr. Ravikant sir
Government PG college Noida
Department of chemistry
aBstract:The emergence of diverse inflections world wide, which is a serious global threat to
human existence, necessitates the urgent development of novel therapeutic candidates
that can been established as an efficient technique in designing bioactive molecules
capable of diverse biological properties can be modified at different positions leading to
the creation of novel drug targets is an active of medical chemistry. This review
containing published articles from 2005 to 2022 highlights isatin hybrid which can have
been synthesized and reported in the literature along side a discussion their biological
properties. The enriched structure – activity relationship studio discussed provii insight
for the ration design of novel isatin hybrid with tailored biological properties as effective
therapeutic candidates inspired by nature.
IntroDuctIon :-
Isatin 1 (indole -2,3-dione :fig1), a secondary metabolite of tryptophan, has been found
to be wildly distributed in the central nervous system, mammalian tissue and body fluids
of humans (1,3), This oxidized indole has been used to the core structure in the
formulation of several compounds which have been tested and identified as potent inhi
of Apoptosis (4-9), Anticovulsants (10,11), antiviral (5, 12 -16), antitubercular (17 -19),
antifungal (20,21), antimicrobial (22,23), antioxidant (24,25), antimalarial(26,27), and
Anti-inflammatory agents (28,29), Among the known heterocyclic compounds, quinoline
and its derivative have been used for the development of novel drug entities, thus gaining
significant attention among 21&t century scientist (30). Triazole hybrid compounds and
aminoquinoline and derivative have shown promise in the development of heart
generation antimalarial (31,32). Xanthone conjugated amino acids, Nmethylpicolinamids , and dihydrazones were recently shown to proray anti-cancer (3335), while dihydrazones analogs have shown promise as potential antibacterial (36).
Isatin is also considered a versatile and favorable precursor for pharmacophor
development as a privileged scaffold (9) because the moiety can be modified at Various
positions (N-1, C-3,C-5 and C-7 positions) as illustrated in fig.1, resulting in different
derivative with diverse biological properties (37,38). The modifications at the N-1, C-3 and
C-5 positions are much more favorable with the mono-substitution at the C-5 positions
considered the most favorable. The C-5 positions considered the most favorable. The C5 positions is beneficial to control the electronic effect, lipophilicity and
physicochemical property. Recently, some isatin – containing compounds have been
approved for clin
ical trials ( sunitinib and Toceranib) (17) used in the treatment of tomors , while others
(Nintedanib , semaxinib, and Orantinib) are currently undergoing clinical trials for the
evaluation of their therapeutic activities, Nintedanib agents (2). This triple angiokinase
inhibitor, Nintedanib indicator for the treatment of idiopathic pulmonary fibrosis,
systematic sclerosis – associated interstitial lungi disease and in combination with
docetaxel for non- small cell lung cancer is a hybrid of indole and piperazine
pharmacophores , sunitinib , a receptor tyrosine kinase inhibitors, and
chemotherapeutic agents is used for the treatment of renal cell carcinoma (RCC) and
imatinib – resistance gastrointestinal stromal tumor (GIST) is a hybrid of isatin and
pyrrole pharmacophores. The development of a singal hybrid compounds by combining
two or more pharmacophores has been proven to be a promising approach in the
development of new drugs that have the potential to overcome drug resistance and
passes improved activity when compared to parents drugs.(35). It is therefore plausible
that the molecules hybridization of the isatin moiety with other pharmacophores has the
potential to generate new or more effective therapeutic candidates (8). There exists
several isatin hybrid molecules generated by the combination of isatin moiety with other
useful pharmaco phores that have outstanding bio- logical activities.
Fig :2
fig:3
Fig :4.
Fig :5
Fig : 6
fig :7
Important class of IsatIn :Isatin , also known as tribulin , is an organic compounds derived from indole with formula
C8H5-NO2. The compounds was first obtained by otto Linne Erdman(1) and Auguste Laurent
(2) in 1840 as a product from the Oxidation of indigo dye by nitric acid and chronic acids.
Name – preferred IUPAC Name
1 H -Indole – 2,3 – dione
IDentIfIers:-
• cas numBer.
91-56-5
• 3D moDel Jsmol.
InteractIve Image
• BeIlsteIn reference.
383659
• cheBI
cheB: 27539
• chemBl.
chemBl 326294
• chem spIDer.
6787
• Drug Bank.
DBo 2095
• echa Into carD.
100.001.889
• ec numBer.
202-077-8
• gmelIn reference.
165206
• ke gg.
c11129
• puB chem cID.
7054
• unII.
82X95s7m06
• comp toX DashBoarD (epa).
DtXsID303894
• InchI.
(show)
• smIles.
(show)
propertIes:-
• chemIcal formula.
c8h5-no2
• molar mass.
147.1308gl mol
• appearance.
orange -reD solID
• meltIng poInt.
200c (392 f , 473k)
BIologIcal applIcatIon’s of IsatIn :1. antI – cancer:Anti- cancer activity in the present scenario , cancer has become a fast growing threat
across the globe. According to the WHO global Observatory report of 2015.about 8.8
million people world wide have died from cancer. It is cases world wide and 17million
cancer deaths in per year. There fore , it is a huge challenge for the researchers to develop
novel effective anti-cancer agents that Offers both selectively as well as lower toxicity.
The anti- cancer activity of isatin and it’s derivative has been widely
explored by researchers.. Interestingly isatin is an important pharmacophores unit in two
clinically approved anti-cancer drugs sunitinib V and Toceranib phosphate.
2. . antI-BacterIal:Isatin derivative display therapeutic potential a variety of pathogenic microbes and are being
wildly explored by researchers for anti- bacterial activity, In Several studies , that 5- halogenation
, N-alkylation. , Nd N – Mannich bases are also effective in causing marked enhancement in the
anti-bacterial activity , A Series of Schiff bases of isatin. Were Synthesized and Screened for
their in vitro anti- bacterial and anti-fungal activities gram positions (staphylococcus aureus and
Bacillus subtitles), gram negative ( Escherichia coli and Proteis vulgaris) bacterial and fungi
(candidates ibicans).
3. antI-DIaBetIc:Anti – diabetic activity Diabetes mellitus (OM), commonly referred to as diabetic,
is a syndrome characterized by disordered metabolism and in appropriately. high
blood sugar (hyperglycemia) resulting either from either low levels of the insulin
hormone or from abnormal of the compound 1- (4-dimethylamino) benzylidene )
-5-(2-Oxoindolin -3). Type 2diabetices is a more common from of world wide, aGlucosidase , a carbohydrates enzyme secreted from the intestinal chorio ic
epithelium, is a therapeutic target for type 2 diabetes. A number of Chromone and
isatin Derivatives have been reported as a- Glucosidase inhibitors.
4. antI- vIral:Anti-viral activity HIV-1(Human immunodeficiency virus type -1) is the widespread type
of virus. The current approvel treatment for the inflections is based on the highly active
anti-retroviral therapy (HAART) , which is a combination of many antiviral agents ,
targeting different steps of the virus repo. Isatin based molecular hybrid have been
reported as duel inhibitors of RT associated enzymatic functions.In a recent study of HIV
-1 Reverse Transcription.
Drugs lIst :Isatin is an active MAOI with dopaminergic properties. A patent had been issued for the
medical use of this compounds.
Isatin is obviously used to Synthesis a plethora of different drugs.
IncluDeD Is a lIst of such agents :
MDA -19 & BZO – CHMOXIZID
Indirubin
Pirquinozol
Tacrine &. Bunricaine (316-15-4)
Cictazindol
funapide
Methisazone. &. Bisatin. (4553-10-0)
Oxyphenistin & hence cofisatine (54063- 34-2)
MeBIO Aldoxime FG: (667463-95-8) Hydroxy tautomer shift( 710323-61-8)
6BIO( 667463-62-9)
Supercinnamaldehyde (70351-51-8)
HT- 2157(SNAP 37889) [303149-14-9]
SNAP.
398299 [. 903878-06-8]
Indigo (Indigotin) [ 482-89-3]
Indirubin
VU0119498 [ 79183-37-2]
references:1. Medvedev A, Buneva O, Gnedenko O, Ershov P, Ivanov A, et
al. (2018) Isatin, an endogenous ho peptide biofactor.
A review of its molecular targets, mechanism of actions and
their biological implications Biofactors
2. Sumrra SH, Atif AH, Zafar MN, Khalid M, THir MN, et al.
(2018) Synthesis, crystal structure, spectral and DFT studies
of potent isatin derived metal complexes J Mol struct 1166.
3.
Havrylyuk D, Zimenkovsky B, Vaslenko O, Gzella A, Leayk
R, et al. (2012) Synthesis of new 4- Thiazolidinone , pyrazoine
and isatin – Based conjugated with promising Antitumor
Activity, Journal Medicinal chemistry.
4. Da Silva JFM , Garden SJ, pinto AC (2001) The chemistry of
isatin a review from 1975 to 1999. J Braz chem Soc.
5. Medvedev AE, Clow A , Sandler M, Glover V (1996) isatin: A
link between natriubnetic pesticides and monoamines?
Biochemical Pharmacology.
6. Bouhfid R, Joly N, Essassi. EM , Lequart V, Massaui M, et al.
(2011) Synthesis of new spiro [1,4,2-dioxazole – 5, 3- indolin]
-2-one
by
1,3-Dipolar
Cycloaddition
synthesis
communication.
7. Nouri MS, O Brien JD, Champa ZJ, Deusakar SP, Lanier OJ, et
al. (2017) Phenylmethimazole and thiazole derivative of
phenylmethimazole inhibitor H-6 expression by negative
breast Cancer cells. European Journal of Pharmacology.
8. Abdelhamid
AO,
Gomha
SM
(2017)
synthesis
and
characterization of new pyrazole -based thiazoles, synthesis
communication
9. Ullah A, Mangi AA, Khan H, Khan B, Nawaz T et al. Formulation
of Locaprofen Micro particles and it’s In vitro charay Lat Am J
Pharm.
10.
Fadda AA, Afsan ESM, Awad Rs(2013) synthesis
antimicrobial activity of some new benzo and hapthonitrile
derivatives.