Browsing by Author "Kumar, Dalip"

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2-(3'-Indolyl)-N-arylthiazole-4-carboxamides: Synthesis and evaluation of antibacterial and anticancer activities
(Elsiever, 2015-10) Kumar, Dalip; Kumar, Anil
A new series of 2-(3′-indolyl)-N-arylthiazole-4-carboxamides 17a–p has been designed and synthesized. Initial reaction of readily available thioamides 15 with bromopyruvic acid under refluxing conditions produced different thiazole carboxylic acids 16 which upon coupling with arylamines by using EDCI·HCl and HOBt afforded diverse arylthiazole-4-carboxamides 17a–p in 78–87% yields. Antibacterial activity evaluation against Gram-positive and Gram-negative bacterial strains led to compounds 17i–k and 17o as potent and selectively (Gram-negative) antibacterial agents. The cytotoxicity of thiazole carboxamides 17a–p was also evaluated on a panel of human cancer cell lines. Among the tested derivatives, compounds 17i (IC50 = 8.64 μM; HEK293T) and 17l (IC50 = 3.41 μM; HeLa) were identified as the most potent analogues of the series. Preliminary mechanism of action studies of thiazole carboxamide 17i suggested that its cytotoxicity against HeLa cells involves the induction of cell death by apoptosis.
Access to 2-Arylindoles via Decarboxylative C−C Coupling in Aqueous Medium and to Heteroaryl Carboxylates under Base-Free Conditions using Diaryliodonium Salts
(Wiley, 2016-10-13) Kumar, Dalip
Diaryliodonium salts have been successfully employed to construct 2-arylindoles and heteroaryl carboxylates. The indoles are prepared using decarboxylative C−C coupling strategy in water. The carboxylates are produced under base-free conditions
Asymmetric Synthesis of Bridged N-Heterocycles with Tertiary Carbon Center through Barbas Dienamine-Catalysis: Scope and Applications
(ACS, 2021-11) Kumar, Indresh; Kumar, Dalip
A direct aza-Diels–Alder reaction between 2-aryl-3H-indolin-3-ones and cyclic-enones has been developed to access chiral indolin-3-one fused polycyclic bridged compounds. This method proceeds via proline-catalyzed Barbas-dienamine intermediate formation from various cyclic-enones such as 2-cyclopenten-1-one, 2-cyclohexene-1-one, and 2-cycloheptene-1-one, followed by a reaction with 2-aryl-3H-indol-3-ones. Several indolin-3-ones fusing [2.2.2], [2.2.1], and [3.2.1] skeletons decorated with a tertiary carbon chiral center have been prepared. Computational studies (DFT) supported the observed stereoselectivity in the method. The synthesized compounds have shown exciting photophysical activities and selective sensing of Pd2+ and Fe3+ ions through the fluorescence quenching “switch-off” mode.
Au-Catalyzed Synthesis of Thiopyrano[2,3-b]indoles Featuring Tandem Rearrangement and Hydroarylation
(ACS, 2017) Kumar, Anil; Kumar, Dalip
Gold(III)-catalyzed synthesis of 14-π electron heteroaromatic thiopyrano[2,3-b]indole is reported using conjugated enyne tethered indole sulfides, featuring skeletal rearrangement conjoined with intramolecular hydroarylation (via C3–H functionalization of the indole core) and oxidative aromatization. Subsequent Pd-catalyzed C–C coupling resulted in a 16-π electron heteroaromatic isothiochromeno[1,8,7-bcd]indole.
BODIPY(aryl)iodonium salts in the efficient synthesis of diversely functionalized BODIPYs and selective detection of serum albumin
(RSC, 2024-04) Kumar, Dalip; Sarkar, Madhushree
BODIPY(aryl)iodonium salts were readily accessible from the high-yielding reaction of BODIPY with iodoarenes or hydroxyl(tosyloxy)iodoarenes in the presence of m-CPBA. The prepared BODIPY(aryl)iodonium salts bearing substituents of varied electronic nature were utilized for the direct syntheses of thiocyanate, azide, amine and acrylate functionalized BODIPYs and β,β′-bis-BODIPYs. The regioselective syntheses of α-piperidinyl and β-piperidinyl substituted BODIPYs were achieved through the reaction of BODIPY(aryl)iodonium salts with piperidine in the absence and presence of copper(I). Expeditious and high yielding (79–82%) synthesis of β,β′-bis-BODIPYs was also developed through the palladium-catalyzed reductive coupling of the easily accessible BODIPY(aryl)iodonium salts. Some of the indole-appended BODIPYs and bis-BODIPYs displayed strong absorption in the visible region (∼610 nm). The BODIPY(aryl)iodonium salts also showed significant binding with serum albumin and were observed to be selective serum protein sensors with estimated limits of detection as low as 7 μg mL−1 in some cases.
C–H arylation of azaheterocycles: a direct ligand-free and Cu-catalyzed approach using diaryliodonium salts
(RSC, 2014) Kumar, Dalip
An efficient and high yielding Cu-catalyzed direct C–H arylation of azaheterocycles including oxadiazoles, thiadiazoles, benzoxazoles and benzothiazoles has been achieved by employing easily accessible diaryliodonium salts.
Cationic porphyrin–quinoxaline conjugate as a photochemically triggered novel cytotoxic agent
(Elsiever, 2013-06) Kumar, Dalip
A novel cationic porphyrin–quinoxaline conjugate 8 was prepared in good yield by the coupling of activated quinoxaline carboxylic acid 5 with an appropriate aminoporphyrin. The UV–vis spectra of conjugate 8 with the addition of ctDNA shows substantial hypochromicity (39%) and a red shift (12 nm) in the Soret band indicating intercalation and self stacking along the surface. The binding constant of conjugate 8 with ctDNA was determined to be 1.26 × 106 M−1. The porphyrin–quinoxaline conjugate 8 displayed enhanced photocytotoxicity (IC50 = 0.06 μM) when compared to TMPyP against A549 cancer cells.
Chemical synthesis in aqueous media using microwaves
(Microwave Symposium Proceedings,, 2006) Kumar, Dalip
The development of efficient, selective and eco-friendly synthetic methods has remained a major focus of our research group. Microwave (MW) irradiation as alternative energy source in conjunction with water as reaction media has proven to be a successful 'greener' chemical approach. The N-alkylation of amines by alkyl halides that proceeds expeditiously in the presence of aqueous NaOH to deliver tertiary amines and double N-alkylation of amines and hydrazine derivatives to assemble a series of heterocyclic moieties such as N-azacycloalkanes, 4,5-dihydropyrazoles and pyrazolidines etc. will be discussed as an environmentally friendlier alternative. An efficient and clean MW-assisted synthesis of alkyl azides/thiocynates will be described by reacting alkyl halides/tosylates with alkali azides/thiocynates. The salient features of using this strategy include considerable reduction in reaction times, minimization or elimination of byproduct formation and improved tolerance for functional groups such as carbonyl, hydroxyl and esters.
ChemInform Abstract: Formation and Dehydration of a Series of 5-Hydroxy-5-trifluoromethyl-4,5-dihydropyrazoles
(Wiley, 2010-06-13) Kumar, Dalip
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Hypervalent Iodine-Mediated Ring Contraction of 2-Arylidenecycloalkanones: A Facile Synthesis of 2-Arylidenecycloalkane Carboxylates
(Wiley, 2010-06-12) Kumar, Dalip
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis of a Heterocyclic Aza-Enediyne and Its DNA-Cleavage Properties
(Wiley, 2010-05-30) Kumar, Dalip
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Chemoselective Cu-catalyzed synthesis of diverse N-arylindole carboxamides, β-oxo amides and N-arylindole-3-carbonitriles using diaryliodonium salts
(RSC, 2024-09) Kumar, Dalip
Chemoselective copper-catalyzed synthesis of diverse N-arylindole-3-carboxamides, β-oxo amides and N-arylindole-3-carbonitriles from readily accessible indole-3-carbonitriles, α-cyano ketones and diaryliodonium salts has been developed. Diverse N-arylindole-3-carboxamides and β-oxo amides were successfully achieved in high yields under copper-catalyzed neutral reaction conditions, and the addition of an organic base (DIPEA) resulted in a completely different selectivity pattern to produce N-arylindole-3-carbonitriles. Moreover, the importance of the developed methodology was realized by the synthesis of indoloquinolones and N-((1H-indol-3-yl)methyl)aniline and by a single-step gram-scale synthesis of the naturally occurring cephalandole A analogue.
Chemoselective Cu-catalyzed synthesis of diverse N-arylindole carboxamides, β-oxo amides and N-arylindole-3-carbonitriles using diaryliodonium salts
(RSC, 2021) Kumar, Dalip
Chemoselective copper-catalyzed synthesis of diverse N-arylindole-3-carboxamides, β-oxo amides and N-arylindole-3-carbonitriles from readily accessible indole-3-carbonitriles, α-cyano ketones and diaryliodonium salts has been developed. Diverse N-arylindole-3-carboxamides and β-oxo amides were successfully achieved in high yields under copper-catalyzed neutral reaction conditions, and the addition of an organic base (DIPEA) resulted in a completely different selectivity pattern to produce N-arylindole-3-carbonitriles. Moreover, the importance of the developed methodology was realized by the synthesis of indoloquinolones and N-((1H-indol-3-yl)methyl)aniline and by a single-step gram-scale synthesis of the naturally occurring cephalandole A analogue.
Click chemistry inspired one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles and their Src kinase inhibitory activity
(Elsiever, 2011-01) Kumar, Anil; Kumar, Dalip
Two classes of 1,4-disubstituted 1,2,3-triazoles were synthesized using one-pot reaction of α-tosyloxy ketones/α-halo ketones, sodium azide, and terminal alkynes in the presence of aq PEG (1:1, v/v) using the click chemistry approach and evaluated for Src kinase inhibitory activity. Structure–activity relationship analysis demonstrated that insertion of C6H5– and 4-CH3C6H4– at position 4 for both classes and less bulkier aromatic group at position 1 in class 1 contribute critically to the modest Src inhibition activity (IC50 = 32–43 μM) of 1,4-disubstituted 1,2,3-triazoles.
A Comparative QSAR Study on Carbonic Anhydrase and Matrix Metalloproteinase Inhibition by Sulfonylated Amino Acid Hydroxamates
(Taylor & Francis, 2008-09-30) Kumar, Dalip; Gupta, S.P.
A quantitative structure-activity relationship (QSAR) study is made on the inhibition of a few isozymes of carbonic anhydrase (CA) and some matrix metalloproteinases (MMPs), both zinc-containing families of enzymes, by sulfonylated amino acid hydroxamates. For both enzymes, the inhibition potency of the hydroxamates is found to be well correlated with Kier's first-order valence molecular connectivity index 1χv of the molecule and electrotopological state indices of some atoms. From the results, it is suggested that while hydroxamate-CA binding may involve mostly polar interactions, hydroxamate-MMP and hydroxamate-ChC (ChC: Clostridium histolyticum collagenase, another zinc enzyme related to MMPs) bindings may involve some hydrophobic interactions. Both MMPs and ChC also possess some electronic sites of exactly opposite nature to the corresponding sites in CAs. A group such as C 6 F 5 present in the sulfonyl moiety is shown to be advantageous in both CA and MMP (also ChC) inhibitions, which is supposed to be due to the interaction of this group with Zn 2+ ion present in the catalytic site of both families of enzymes.
Conformation and ortho steric effects in a series of 2-(pyrazol-1-yl)quinolines
(Wiley, 1996-04) Kumar, Dalip
Nine 2-(pyrazol-1-yl)-4-methylquinolines bearing substituents on the pyrazole 3- or 5-positions (H, Me, Et, i-Pr, t-Bu) were regioselectively synthesized either using the direct condensation of 2-chloro-4-methylquinoline and sodium salt of 3(5)-substituted pyrazoles or by treatment of 2-hydrazino-4-methylquinoline with an appropriate β-ketoaldehyde. The 1H and 13C chemical shifts were discussed taking into account the preferred conformation about the C-2-N-1′ bond as calculated by the AM1 Hamiltonian. It appears that 5-ethyl and 5-isopropyl substituted derivatives present short C-H-N-1 interactions. Ortho steric effects appear to be responsible for these conformations.
Conjugation of a hairpin pyrrole-imidazole polyamide to a quinone methide for control of DNA cross-linking
(ACS, 2004-06) Kumar, Dalip
A series of quinone methide precursors designed for DNA cross-linking were prepared and conjugated to a pyrrole-imidazole polyamide for selective association to the minor groove. Although reaction was only observed for DNA containing the predicted recognition sequence, yields of strand alkylation were low. Interstrand cross-linking was more efficient than alkylation but still quite modest and equivalent to that generated by a comparable conjugate containing the N-mustard chlorambucil. Varying the length of the linker connecting the polyamide and quinone methide derivative did not greatly affect the yield of DNA cross-linking. Instead, intramolecular trapping of the quinone methide intermediate by nucleophiles of the attached polyamide appears to be the major determinant that limits its reaction with DNA. Self-adducts of the quinone methide conjugate form readily and irreversibly as detected by a combination of chromatography and mass spectroscopy. This result is unlike comparable self-adducts observed for oligonucleotide conjugates that form more slowly and remain reversible. Equivalent intramolecular alkylation of a polyamide by its attached chlorambucil mustard was not observed under similar condition. The presence of DNA, however, did facilitate hydrolysis of this mustard conjugate.
Conjugation of a Hairpin Pyrrole-Imidazole Polyamide to a Quinone Methide for Control of DNA Cross-Linking
(ACS, 2004) Kumar, Dalip
A series of quinone methide precursors designed for DNA cross-linking were prepared and conjugated to a pyrrole-imidazole polyamide for selective association to the minor groove. Although reaction was only observed for DNA containing the predicted recognition sequence, yields of strand alkylation were low. Interstrand cross-linking was more efficient than alkylation but still quite modest and equivalent to that generated by a comparable conjugate containing the N-mustard chlorambucil. Varying the length of the linker connecting the polyamide and quinone methide derivative did not greatly affect the yield of DNA cross-linking. Instead, intramolecular trapping of the quinone methide intermediate by nucleophiles of the attached polyamide appears to be the major determinant that limits its reaction with DNA. Self-adducts of the quinone methide conjugate form readily and irreversibly as detected by a combination of chromatography and mass spectroscopy. This result is unlike comparable self-adducts observed for oligonucleotide conjugates that form more slowly and remain reversible. Equivalent intramolecular alkylation of a polyamide by its attached chlorambucil mustard was not observed under similar condition. The presence of DNA, however, did facilitate hydrolysis of this mustard conjugate.
Conjugation of a Hairpin Pyrrole-Imidazole Polyamide to a Quinone Methide for Control of DNA Cross-Linking
(ACS, 2004) Kumar, Dalip
A series of quinone methide precursors designed for DNA cross-linking were prepared and conjugated to a pyrrole-imidazole polyamide for selective association to the minor groove. Although reaction was only observed for DNA containing the predicted recognition sequence, yields of strand alkylation were low. Interstrand cross-linking was more efficient than alkylation but still quite modest and equivalent to that generated by a comparable conjugate containing the N-mustard chlorambucil. Varying the length of the linker connecting the polyamide and quinone methide derivative did not greatly affect the yield of DNA cross-linking. Instead, intramolecular trapping of the quinone methide intermediate by nucleophiles of the attached polyamide appears to be the major determinant that limits its reaction with DNA. Self-adducts of the quinone methide conjugate form readily and irreversibly as detected by a combination of chromatography and mass spectroscopy. This result is unlike comparable self-adducts observed for oligonucleotide conjugates that form more slowly and remain reversible. Equivalent intramolecular alkylation of a polyamide by its attached chlorambucil mustard was not observed under similar condition. The presence of DNA, however, did facilitate hydrolysis of this mustard conjugate.
A Convenient and Facile Synthesis of Naturally Occurring 2,5-Diaryloxazoles
(ISCB, 2012-07) Kumar, Dalip
A facile and high yielding synthesis of naturally occurring 2,5-diaryloxazoles including annuloline, balsoxin, texamine and texaline, has been reported. The protocol involves initial reaction of [hydroxy(tosyloxy)iodo] benzene with enolizable ketones to prepare α-tosyloxy ketones, which upon treatment with HMTA and followed by hydrolysis in presence of hydrochloric acid led to α-amino ketones in fairly good yields. Acylation of α-amino ketones produced α-acylamino ketones which upon cyclodehydration in presence of triphenylphosphine and iodine led to 2,5-diaryloxazoles in very good yields .