
Manojit Pal- PhD FRSC
- Senior Professor at Dr Reddy's Institute of Life Sciences, University of Hyderabad
Manojit Pal
- PhD FRSC
- Senior Professor at Dr Reddy's Institute of Life Sciences, University of Hyderabad
About
413
Publications
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Introduction
Current research interest
Med Chem: Design and synthesis of new chemical entities in the following therapeutic areas (1) cancer (sirtuin inhibitors) (2) tuberculosis (Chorismate mutase inhibitors) (3) inflammation (PDE-4, LOX inhibitors) (4) Metabolic disorder & obesity (GPCRs)
Organic Chem: (1) heterocyclic chemistry (2) transition metal / lanthanides /rare earth / clay catalyzed reactions (3) multi-component reactions (4) green chemistry – zip / domino / cascade reactions, C-H/amino group activation (4) Ultrasound assisted reactions (5) synthesis of compounds related to natural products etc
Methods and techniques
(1) Use of Pd/C beyond hydrogenation (2) Use of AlCl3 beyond Friedel Crafts reaction (3) use of modern synthetic methodologies for novel heteroaromatics
Current institution
Dr Reddy's Institute of Life Sciences, University of Hyderabad
Current position
- Senior Professor
Additional affiliations
August 2018 - present
May 2009 - present
Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad
Position
- Head of Faculty
Description
- Design and synthesis of new chemical entities in the following therapeutic areas (1) cancer (2) tuberculosis (3) inflammation (4) metabolic disorder & obesity
Publications
Publications (413)
The search for new anti-tubercular agents is vital for the fight against Mycobacterium tuberculosis, particularly given the rise of drug-resistant strains. DRILS-1398, a pyrazolo[4,3-d]pyrimidine derivative, was discovered as a potent inhibitor of M.tb chorismate mutase (M.tb-CM) with an IC50 = 3.0 ± 0.2 μM (n = 3) and IC90 = 10 μM. The compound de...
Bioorganic Chemistry predominantly signifies the study or research activities in the area of Organic Chemistry-Biology interface that are aim to address biological questions at the molecular level with the help of organic chemistry particularly organic synthesis. The green and sustainable synthetic approaches are in great demand because they reduce...
The simple yet innovative synthetic approaches for the direct access to the diversity based unique class of compounds of potential biological interest are of considerable interest as that can greatly facilitate the efforts in bioorganic / medicinal chemistry and drug discovery. In our efforts, we have developed a metal-free, inexpensive and one-pot...
The reported antiviral properties of isoquinolines including that of berberine against dengue virus prompted us exploring a series of 1‐aminoisoquinoline derivatives against RdRp and MTase domain of NS5 protein of dengue virus (DENV) in silico. While MTase is known to assists in viral RNA capping, the RdRp plays a key role in the virus replication....
The Wang‐OSO3H catalyzed synthesis of a series of spiroindoline‐3,2’‐quinazoline derivatives and their in silico and in vitro evaluation against MtbCM (Mycobacterium tuberculosis Chorismate Mutase) are disclosed. Initially, a library of small molecules based on spiroindoline‐3,2’‐quinazoline framework was constructed. The reaction of 2‐aminobenzami...
https://research.com/university/chemistry/university-of-hyderabad
The in silico evaluation of 11H-pyrido[2,1-b]quinazolin-11-one derivatives against SARS-CoV-2 RdRp was undertaken based on the reports on antiviral activities of this class of compounds in addition to the promising interactions of the antiviral drug penciclovir as well as quinazoline derivatives with SARS-CoV-2 RdRp in silico. The target compounds...
The 12R-lipoxygenase (12R-LOX), a (non-heme) iron-containing metalloenzyme belonging to the lipoxygenase (LOX) family catalyzes the conversion of arachidonic acid (AA) to its key metabolites. Studies suggested that 12R-LOX plays a critical role in immune modulation for the maintenance of skin homeostasis and therefore can be considered as a potenti...
Green or environmentally friendly synthetic approaches (including transition metal catalyzed reactions) are in high demand in organic synthesis because they can reduce or eliminate the application or generation of hazardous substances, thereby promising to limit environmental pollution to a great extent. Medicinal chemistry, on the other hand, is a...
The enzyme chorismate mutase (or CM that is vital for the survival of bacteria) is an interesting pharmacological target for the identification of new anti-tubercular agents. The 5,5-disibstituted pyrazolo[4,3-d]pyrimidinone derivatives containing the fragment based on 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide were designed and explored a...
The importance of the quinoxaline framework is exemplified by its presence in the well-known drugs such as varenicline, brimonidine, quinacillin, etc. In the past few years, preparation of a variety of organic compounds containing the quinoxaline framework has been reported by several research groups. The chloroquinoxalines were successfully used a...
Efforts have been devoted for the discovery and development of positive allosteric modulators (PAMs) of 5-HT2CR because of their potential advantages over the orthosteric agonist like Lorcaserin that was withdrawn from the market. On the other hand, pursuing a positive ago-allosteric modulator (PAAM) is considered as beneficial particularly when an...
The 5-substituted 7-amino-6-cyano-1,5-dihydro-2H-pyrano[2,3-d]pyrimidine-2,4(3H)-diones were explored for their potential inhibitory properties against SIRT1 (Sirtuin 1). The rapid access to this class of compounds was achieved via a sonochemical approach involving the Wang-OSO3H catalyzed three component reaction of barbituric acid, aromatic aldeh...
In the current study we have demonstrated the effectiveness of ultrasound, a source of green energy, in accessing various isoquinolin‐1(2H)‐one derivatives via the sequential two‐step reaction in a single pot. The methodology involved ultrasound assisted Cu‐catalyzed α‐arylation of ketones with 2‐iodobenzamide (via a C−C bond formation) followed by...
Mycobacterium tuberculosis (Mtb) is a pathogen of major concern due to its ability to withstand both first- and second-line antibiotics, leading to drug resistance. Thus, there is a critical need for identification of novel anti-tuberculosis agents targeting Mtb-specific proteins. The ceaseless search for novel antimicrobial agents to combat drug-r...
Based on the known link of inflammation with the diseases (especially cancer) for which pyrimido[1,2-b]indazoles have been explored previously, the anti-inflammatory potential of this class of compounds were assessed in the current study. Initially, the feasibility of this idea was examined with the help of in silico docking studies using TNF-α as...
Because of importance of the quinazolinone framework particularly in medicinal and pharmaceutical chemistry efforts have been devoted to establish convenient methods for the synthesis of quinazolinone derivatives. Due to our interest in this class of compounds as potential inhibitor chorismate mutase (MtbCM), a known target for the identification o...
In view of the reported chorismate mutase (CM or MtbCM) inhibitory activities of 3-indolylmethyl substituted (pyrazolo/benzo)triazinone derivatives the structurally similar 3-(benzofuran-2-ylmethyl) substituted (pyrazolo/benzo)triazinones were designed and evaluated in silico against CM. The docking of target molecules was performed at the interfac...
Besides its use against HIV infection the marketed anti-retroviral drug dolutegravir attracted attention as a potential agent against COVID-19 in multiple AI (artificial intelligence) based studies. Due to our interest in accessing the impurities of this drug we report the synthesis and characterization of three impurities of dolutegravir one of wh...
The pyrano[2,3-c]pyrazole framework was explored for the design and synthesis of compounds as potential inhibitors of SIRT1. The feasibility of this strategy was reasoned by the unique structural features of this scaffold and the reported cytotoxicity of compounds containing this framework. The sonochemical synthesis of target compounds was accompl...
Dolutegravir is a fluorine containing antiretroviral drug prescribed for the treatment of HIV infection in combination with other HIV medicines in adults. Its chemical synthesis is associated with the formation of several impurities including the Enantiomer (4S, 12aR), Impurity B, and Ethoxy acetamide the synthesis of which are presented here. The...
Encouraged by the reported sirtuin modulating ability of an imidazopyridazine derivative the structurally relevant imidazo[1,2-a]pyridine framework was explored for the design and synthesis of prospective inhibitors of sirtuins. The synthesis of targeted imidazo[1,2-a]pyridine derivatives was carried out via a NBS (N-bromosuccinimide) promoted reac...
Addressing the increasing incidences of cancer worldwide along with the multifaceted problem of drug resistance via development of new anticancer agents has become an essential goal. Due to the known cytotoxic effects and reported Akt inhibitory potential of azaindoles we designed a new framework incorporating the structural features of rosuvastati...
Because of important role in cancer, sirtuins especially the SIRT1 is viewed as an interesting pharmacological target for developing potential anticancer agents. Based on our previous studies on sirtuin inhibitory potential of 1,8-dioxodecahydroacridines we extended our efforts towards exploring the structurally relevant 1,8-dioxo-octahydroxanthene...
In search of potent and new anti-inflammatory agents, we explored a new class of isocoumarin derivatives possessing the 3-oxoalkyl moiety at C-4 position. These compounds were synthesized via the FeCl3 catalyzed construction of isocoumarin ring. The methodology involved coupling of 2-alkynyl benzamides with alkyl vinyl ketone and proceeded via a re...
In spite of various and extensive studies known for pyrazolo[1,5-a]pyrimidines the synthesis, in silico studies and biological evaluation of their 5-(het)aryl analogs remained underexplored. The TNF-α inhibitors on the other hand has considerable therapeutic potential for autoimmune and inflammatory diseases in addition to cancer, diabetes and poss...
A rapid synthesis of isocoumarins has been achieved via the Cu-catalysed cascade reaction involving tandem intramolecular cyclization followed by olefin addition under ultrasound irradiation. The methodology involved one-pot reaction of 2-alkynylbenzoate esters with methyl vinyl ketone in the presence of Cu(OAc)2 in aqueous DMF to afford a range of...
For the first time SnCl 2 ·2H 2 O has been identified as a convenient precatalyst for the synthesis of pyridine derivatives via an MCR in water. The 4-component reaction of alkyl / (hetero)aryl aldehydes, b-keto esters (or 1,3-diketones), anilines and malononitrile afforded a range of new polysubstituted pyridines including 4-alkyl/heteroaryl deriv...
The study of drug impurities constitutes an important area of process research and development. In the current study the synthesis of two diastereomeric impurities namely R,R- and S,S-isomer of recently approved antiretroviral drug dolutegravir was explored. Accordingly, a simple and scalable process has been developed for the first time for the sy...
New approaches / strategies to develop potential anticancer agents are necessary not only to address the increasing incidences of cancer worldwide but also to overcome the multifaceted problem of drug resistance. SIRT1, the most widely studied among all the sirtuins plays an important role in cancer and is considered as a promising pharmacological...
The sulphonic acid-functionalized Wang resin (Wang-OSO3H) was explored as a polymeric and recoverable acidic catalyst for the synthesis of isoindolo[2,1-a]quinazoline-5,11-dione derivatives under green conditions. Thus the Wang-OSO3H catalyzed MCR of isatoic anhydride, 2-formylbenzoic acid and various amines in pure water afforded a range of desire...
A series of indole based novel Schiff bases was designed as potential agonists of 5‑HT2C receptor that was supported by docking studies in silico. These compounds were synthesized via Amberlyst-15 catalysed condensation of an appropriate pyrazole based primary amine with the corresponding indole-3-aldehyde under ultrasound irradiation at ambient te...
Prompted by the reported HDAC1 inhibition / anticancer properties of 3-methyleneisoindolin-1-one derivatives a series of 3-heteroarylmethylene substituted isoindolin-1-ones were explored as potential inhibitors of SIRT1. A sonochemical approach based on the Cu(I)-catalyzed decarbonylative Sonogashira coupling-cyclization strategy was developed for...
A new and unique indolo[1,2-a]quinoxaline framework has been explored for the identification of potential cytotoxic agents. Thus a series of targeted indolo[1,2-a]quinoxaline derivatives were prepared via an ultrasound assisted MCR of N‐(2‐aminophenyl)indole, isatin and an appropriate alcohol using Amberlyst-15 as a catalyst. The MCR does not requi...
A Pd-catalysed regioselective synthesis of 4,5-disubstituted 7-membered N/O-heterocycles was achieved via the 7-endo-dig cyclization followed by C-C bond formation of 2-(1-alkynyl)phenylacetamide. The ligand/additive free cascade reaction proceeded in the presence of PdCl2 in aqueous MeCN when the separate and individual use of methyl vinyl ketone...
The 2-amino nicotinonitrile framework has been explored first time for the identification of potential inhibitors of SIRT1. Thus a series of targeted 2-amino-4,6-disubstituted nicotinonitrile derivatives were synthesized by employing an ultrasound assisted MCR of ketones, aldehydes, malononitrile and ammonium acetate. The MCR was carried out in the...
In spite of possessing a wide range of pharmacological properties the anti-inflammatory activities of isoquinolin-1(2H)-ones were rarely known or explored earlier. PDE4 inhibitors on the other hand in addition to their usefulness in treating inflammatory diseases have been suggested to attenuate the cytokine storm in COVID-19 especially TNF-α. In o...
Based on the initial docking studies of a representative compound in silico the evaluation of SIRT1 inhibitory potential of 2-substituted nicotinic acid ethyl ester derivatives was undertaken in vitro. A sonochemical method was developed and employed for the faster synthesis of this class of compounds. The methodology involved the iodine-mediated r...
While anti-inflammatory properties of isocoumarins are known their PDE4 inhibitory potential was not explored previously. In our effort the non-PDE4 inhibitor isocoumarins were transformed into the promising inhibitors via introducing an aminosulfonyl/aminocarboxamide moiety to the C-3 benzene ring attached to the isocoumarin framework. This new cl...
The Pd/Cu-catalyzed tandem coupling-cyclization-N-deprotection in a single pot (Method a) vs sequential coupling-cyclization under similar conditions (Method b) has been studied using propargylamine as a terminal alkyne under environmentally friendly conditions. The first sequence (Method a) was followed to afford the N-unsubstituted indoles when 2...
The Sonochemical synthesis of a library of 3-methyleneisoindolin-1-one based novel small molecules derived from rosuvastatin designed as potential anticancer agents was undertaken. A Cu-mediated coupling-cyclization strategy was employed to prepare this new class of compounds in a single pot with notable regioselectivity. The use of a terminal alky...
The ultrasound assisted facile, rapid and one-pot synthesis of 2-aryl substituted 4,5-diphenyloxazoles was achieved via the reaction of commercially available benzoin (or 2-hydroxy-2-phenylacetophenone) with benzylamines in the presence of IBX under mild conditions. The methodology involved initial IBX mediated conversion of benzoin to benzil and t...
The various aspects of past, present, and future of anti-diabetes research in India are covered here. A brief introduction on prevalence of diabetes in India followed by anti-diabetes drugs currently available is presented. Contributions made by various industrial R&Ds and organizations are mainly highlighted with the particular focus on organic mo...
In view of remarkable biological properties including anticancer activities of N‐aryl pyrazoles we have explored N‐(2‐methoxyphenyl) substituted pyrazoles and related derivatives as potential cytotoxic agents. In silico methods were adopted to understand/predict the biochemical and physiological effects, toxicity, and biological profiles of these c...
The recent global pandemic caused by COVID-19 has triggered an intense effort worldwide towards the development of an effective cure for this disease. In our effort we have explored the 2-alkynyl substituted 3-chloropyrazine framework as a potential template for the design of molecules for this purpose. Our strategy was supported by the in silico s...
In view of the recent global pandemic caused by COVID-19 intense efforts have been devoted worldwide towards the development of an effective treatment for this disease. Recently, PDE4 inhibitors have been suggested to attenuate the cytokine storm in COVID-19 especially tumour necrosis factor alpha (TNF-α). In our effort we have explored the 2-subst...
In the current study, we have explored 6‐substituted indolo[3′,2′:4,5]pyrrolo[2,3‐b]quinoxaline derivatives as potential cytotoxic agents. These compounds were readily prepared via the reaction of 2‐chloro‐3‐(2‐chloro‐1H‐indol‐3‐yl)quinoxaline with an appropriate amine under ultrasound irradiation in good to acceptable yields. The in vitro testing...
Background:
The indole framework is considered as one of the privileged structures in the area of medicinal chemistry and drug discovery because compounds containing this framework have shown to possess remarkable ability to bind with many receptors or proteins with high affinity. It is therefore not surprising that indole nucleus is a frequently...
In view of recent global pandemic the 3-alkynyl substituted 2-chloroquinoxaline framework has been explored as a potential template for the design of molecules targeting COVID-19. Initial in silico studies of representative compounds to assess their binding affinities via docking into the N-terminal RNA-binding domain (NTD) of N-protein of SARS-CoV...
Synthesis of polyhydroquinolines via Hantzsch’s multicomponent reaction (MCR) involves the use of a hygroscopic and moderately toxic ammonium salt as one of the key reactants. In our effort we have found urea as an effective ammonia surrogate when the MCR was performed in the presence of sulphonic acid functionalized Wang resin (Wang-OSO3H) as a po...
A new class of 3-substituted isocoumarin/3-alkylidenephthalide based novel small molecules derived from rosuvastatin were designed and synthesized via the ultrasound assisted Cu-mediated coupling-cyclization in a single pot with remarkable regioselectivity. The phthalides were generally obtained at lower temperature whereas the use of elevated temp...
Background:
The 2-amino 1,3,4-thiadiazole framework has attracted considerable interest because of its prevalence in compounds possessing a wide range of pharmacological properties including anticancer / antitumor activities. Though a number of methods have been reported for the synthesis of this class of compounds some of them are not straightfor...
Prompted by the in silico docking study predictions the first β-cyclodextrin (β -CD) mediated synthesis of 4-oxo-4,5,6,7-tetrahydroindoles in water was achieved via a 3-component reaction under neutral conditions. A range of compounds was prepared by using this environmentally friendly method in good yields (82-92%). The catalyst β -CD could be rec...
Background
Compounds containing furo[3,2-b]pyridine framework have shown interesting pharmacological properties including anticancer activities. Though these compounds are generally synthesized via the heteroannulation processes involving acetylenic derivatives some of them are not straightforward.
Objective
To explore a series of 2-substituted fu...
An improved and rapid synthesis of mefenamic acid based indole derivatives has been achieved via the ligand free Cu-catalyzed coupling-cyclization method under ultrasound irradiation. This simple, straightforward and inexpensive one-pot method involved the reaction of a terminal alkyne derived from mefenamic acid with 2-iodosulfanilides in the pres...
bond forming reaction between 2,3-dichloroquinoxaline and. These compounds further indoloquinoxoline via the direct C-H activation and identified as inhibitors for PDE4B (one of the compound showed good inhibition with IC 50~ 0.39 ± 0.13 µM). ABSTRACT CC BOND FORMATION LIST OF COMPOUNDS SYNTHESIZED Indole derivatives having quinoxoline group at C-3...
In spite of their various pharmacological properties the anti-inflammatory potential of benzo[c]phenanthridines remained underexplored. Thus, for the first time PDE4 inhibitory potential of 11,12-dihydro benzo[c]phenanthridine / benzo[c]phenanthridine was assessed in vitro. Elegant synthesis of these compounds was performed via a multi-step sequenc...
Background
The 2-substituted benzofuran framework has attracted enormous attention due to its presence in a range of bioactive compounds and natural products. While various methods for the synthesis of 2-substituted benzofuran derivatives are known several of them suffer from certain drawbacks.
Objective
The main objective of this work was to expl...
A series of novel isatin–indole derivatives has been designed as potential inhibitors of chorismate mutase (CM) that is known to be present in bacteria, fungi and higher plants but not in human. The design was supported by in silico docking studies that predicted strong interactions of these molecules with CM. The target compounds were synthesized...
Background
The oxazolone class of compounds is known to exert profound effect on malignant cell proliferation, tumor angiogenesis and /or on the established neoplastic vasculature. Additionally, these compounds are generally known to have low tendency to interact with DNA which is not common with most of the conventional cytotoxic agents. Thus this...
Ultrasound assisted one-pot and direct access to 1,2-diaryl substituted azaindole derivatives has been achieved via the sequential N-arylation followed by coupling-cyclization under Pd/C-Cu catalysis. The methodology involved initial CN bond forming reaction (step 1) between an appropriate o-bromo substituted amino pyridine and iodoarene followed b...
Background
Compounds containing the quinazoline-4(3H)-one framework constitute an important class of fused N-heterocycles that are found in more than 200 naturally occurring alkaloids. These compounds also show a diverse range of pharmacological activities including antitumor properties. This prompted us to explore a series of quinazolin-4-(3H)-one...
The chorismate mutase (CM) is considered as an attractive target for the identification of potential antitubercular agents due to its absence in animals but not in bacteria. A series of 3-indolylmethyl substituted pyrazolotriazinone derivatives were designed and docked into CM in silico as potential inhibitors. These compounds were efficiently synt...
Hyperbranched polyaromatic polymer (HBP) based on pyridylphenylene dendrimer as a multifunctional monomer was employed as a nanoreactor and a stabilizing matrix for synthesis of catalytic Ni nanoparticles (NPs). The HBP was found to have an effective control over NP size. The Ni NPs synthesized in HBP matrix had diameter between 3 and 4.5 nm with n...
A new class of PDE4 inhibitors were designed and synthesized via the InCl 3 mediated heteroarylation of indoles and their further derivatization through the Pd(II)-catalyzed C[sbnd]H activation strategy. This effort allowed us to discover a series of 2-(1H-indol-3-yl)-quinoxaline based inhibitors possessing PDE4B selectivity over PDE4D and PDE4C. O...
Background:
In view of numerous biological activities of 3-substituted isocoumarins a number of analogues based on this scaffold were synthesized for their in vitro pharmacological evaluation.
Methods:
The syntheses of 3-substituted isocoumarins were carried out via a Pd/C-catalyzed Suzuki- Miyaura coupling of 3-chloroisochromen-1-one with a ran...
Propargylamine (secondary) has been explored as a building block in synthesizing indoles via an ultrasound assisted Pd/Cu-catalyzed coupling-cyclization method. Indoles containing a pyrazole moiety at C-2 attached via the –CH2NH– linker (designed as potential anti-tubercular agents) were synthesized first and then generality/scope of the methodolog...
Background
A non-hazardous synthetic methodology has been developed for the preparation of compounds based on indolofuroquinoxaline framework. Lemon juice that is known to play the role of a biocatalyst in various organic reactions was used for this purpose.
Method
A number of indolofuroquinoxaline derivatives were prepared via the lemon juice med...
Background
The 8-Aminoquinoline (8-AQ) framework has attracted particular attention in the discovery and development of antimalarial and anti-bacterial agents or drugs. However, the clinical uses of 8-AQ based drugs are often associated with toxic side effects such as methemoglobinemia and hemolytic anemia with deficiency in Glucose-6-Phosphate Deh...
The 1,2,3-triazole ring fused with pyridine / pyrimidine was explored as new template for the identification of potential antimicrobial agents. The regioselective synthesis of these pre-designed N-heteroarenes was achieved via exploring the application of Buchwald’s strategy (i.e. C-N bond formation / reduction / diazotization / cyclization sequenc...
A convenient and general method for the synthesis of benzofurans from o-iodophenol and acetylenic compounds under palladium-catalysed conditions is described.
A conceptually new three-component reaction was developed to construct a six-membered fused N-heterocyclic ring affording (pyrazolo)pyrimidines/pyridines as potential inhibitors of PDE4. The reaction is catalyzed by triflic acid in acetic acid in the presence of aerial oxygen.