Abdul Ajees

Manipal Academy of Higher Education | MAHE · Department of Atomic and Molecular Physics

The human toll-like receptor (hTLR) 4 single nucleotide polymorphisms (SNPs) are interconnected with cancer, multiple genetic disorders and other immune-related diseases. The detrimental effect of SNPs in hTLR4 with respect to structure and function has not been explored in depth. The present study concatenates the biological consequences of the SN...

Background: Cereblon, an extensively studied multifunctional protein, is a Cullin 4-RING E3 ubiquitin ligase complex component. Cereblon is a well-known target of thalidomide and its derivatives. Cereblon is involved in multiple myeloma cell apoptosis. When ligands such as thalidomide and lenalidomide bind to cereblon, it recognizes various neosub...

P-glycoprotein (P-gp), a transmembrane glycoprotein, is mainly involved in lung cancer multidrug resistance. Several P-gp inhibitors have been developed to enhance the efficacy of chemotherapeutics and overcome drug resistance. However, most of them failed in the clinical stages due to undesirable side effects. Therefore, there is a requirement to...

Background: Cereblon, an extensively studied multifunctional protein, is a Cullin 4-RING E3 ubiquitin ligase complex component and a well-known target of thalidomide and its derivatives. Cereblon is involved in the apoptosis of multiple myeloma cells. When ligands such as lenalidomide bind to cereblon, it recognizes various neosubstrates based on t...

Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV) is one of Asia's most common viral encephalitis. JEV is a flavivirus, common in rural and sub-urban regions of Asian countries. Although only 1% of JEV-infected individuals develop JE, there is a 20–30% chance of death among these individuals and possible neurological sequel...

Different types of Glutaredoxins (GRXs) that play a major role in cellular anti-oxidative reactions have been studied for their structure and function from various organisms. Glutathione (GSH), an anti-oxidant with several medical benefits, binds to GRXs. This work has structurally characterized GRX2 from C. reinhardtii (CrGRX2) using biophysical,...

3-Benzylchroman-4-ones (homoisoflavanones) are oxygen-containing heterocycles with a sixteen-carbon skeleton. They belong to the class of naturally occurring polyphenolic flavonoids with limited occurrence in nature and possess anti-inflammatory, antibacterial, antihistaminic, antimutagenic, antiviral, and angioprotective properties. Recently, we r...

Biochemical and pharmacological investigations carried out on the small molecule 6b, 11b-Dihydroxy-6b, 11-b-dihydro-7H-indeno[1,2-b]naptho[2,1-d]furan-7-one (DHFO) has shown that it is an analgesic, anti-inflammatory agent, and a dual 5-LOX/COX-2 inhibitor. DHFO is also a free-radical scavenger, a potent antioxidant, and an inhibitor of lipid perox...

The ability of liquid crystalline materials to feature self-assembly behavior has garnered attention in designing new aggregates for various functional applications. The structural influence of hydrogen-donating and accepting moieties on the liquid crystalline behavior of hydrogen-bonded assemblies of guanazole (G) with liquid crystalline nonyloxy...

Background Identification and repurposing of therapeutic and preventive strategies against COVID-19 are rapidly undergoing. Several medicinal plants from the Himalayan region have been traditionally used to treat various human disorders. Thus, in our current study, we intend to explore the potential ability of Himalayan medicinal plant (HMP) bioact...

The conformational flexibilities are studied in two new organotin(IV) complexes, namely, trans-dichloridodimethylbis[N,N',N''-tris(2-chlorobenzyl)phosphoric triamide]tin(IV), [Sn(CH3)2(C21H21Cl3N3OP)2Cl2] or Sn(CH3)2Cl2{OP[NHCH2C6H4(2-Cl)]3}2, (I), and bis(dipropylammonium) tetrachloridodimethylstannate(IV), [(CH3CH2CH2)2NH2]2[Sn(CH3)2Cl4], (II), a...

p53, a tumor suppressor protein has a prominent role in forestalling tumor development and advancement through its involvement in cell division control and initiation of apoptosis. Hence p53 is an attractive drug target. Some alkaloids, xanthones and nutraceuticals have anticancer activities. Herein, berberine, gallic acid, rutin and mangiferin wer...

COVID-19 is an infectious pandemic caused by the SARS-CoV-2 virus. The critical components of SARS-CoV-2 are the spike protein (S-protein) and the main protease (Mpro). Mpro is required for the maturation of the various polyproteins involved in replication and transcription. S-protein helps the SARS-CoV-2 to enter the host cells through the angiote...

Abstract Background Coronavirus disease-(COVID-19) is an infectious pandemic caused by SARS-CoV-2. SARS-CoV-2 main protease (Mpro) and spike protein are crucial for viral replication and transmission. Spike protein recognizes the human ACE2 receptor and transmits SARS-CoV-2 into the human body. Thus, Mpro, spike protein, and ACE2 receptor act as ap...

A small library of hitherto unexplored novel 5-fluorobenzoisoxazolyl-piperidinyl-1, 2, 3-triazole derivatives has been synthesized from 2-azido-fluorobenzoisoxazolyl piperidinyl ethanone and various alkynes in good to excellent yields through a click chemistry approach. Compounds thus synthesized were evaluated for their cytotoxicity against HepG-2...

The establishment of high-tech products relying on organic optoelectronics is focused towards latest strategies for improving the processability and performance. In the present study, two esters of salicylaldehyde azine SAE-F and SAE-NF were synthesized and their structural characterization were performed using FT-IR, ¹H and ¹³C NMR, UV–visible spe...

Electrons and .OH-radicals have been generated by using low-energy laser pulses of 6 ns duration (1064 nm wavelength) to create plasma in a suspension of plasmid DNA (pUC19) in water. Upon thermalization these particles induce single and double strand breakages in DNA along with possible base oxidation/base degradation. The time-evolution of the en...

The crystal structures of diphenyl (cyclo­heptyl­amido)­phosphate, C19H24NO3P or (C6H5O)2P(O)(NHC7H13), (I), and diphenyl (di­benzyl­amido)­phosphate, C26H24NO3P or (C6H5O)2P(O)[N(CH2C6H5)2], (II), are reported. The NHC7H13 group in (I) provides two significant hydrogen-donor sites in N—H...O and C—H...O hydrogen bonds, needed for a one-dimensional...

The title salt, [(C6H11)2NH2][(C6H5O)2P(O)(O)], crystallizes in the chiral space group P212121, composed of achiral cation and anion components. The strong charge-assisted N-H…O hydrogen bonds build a linear assembly along the a axis, including a non-centrosymmetric C22(6) chain graph-set motif. The intra and intermolecular C-H…O interactions as we...

Apoptosis is a vital physiological process, which is observed in various biological events. The anti-apoptotic and pro-apoptotic members of Bcl-2 family are the most characterized proteins which are involved in the regulation of apoptotic cell death. The anti-apoptotic proteins such as Bcl-2 and Bcl-xL prevent apoptosis, whereas pro-apoptotic membe...

The article is available free of cost at the publisher's website until Jan 20, 2019. Link: https://authors.elsevier.com/c/1Y95Uc8qpIhPw Small-molecule organic fluorophores are highly in demand attributed to their extensive prospective in material and biomedical applications. Particularly, luminescent π-conjugated organic molecules that possess a...

Laser-induced crystallization is emerging as an alternative technique to crystallize biomolecules. However, its applications are limited to specific small molecules and some simple proteins, possibly because of the need to use high-intensity, pulsed lasers and relatively long laser irradiation time. Both these factors tend to denature biological mo...

The cdc25 family of phosphatases plays a vital role in cell cycle regulation. The role of CdC25B (one of the isoforms of CdC25) in tumor cell growth is well recognized. All the active site of the CdC25 proteins has the consensus Cys-X5-Arg motif. Based on the three-dimensional structural studies, the role of the cysteine and arginine residues in Cd...

http://scripts.iucr.org/cgi-bin/paper?S2053273317092221

The influence of a N heteroatom on the ring conformations of six- and seven-membered aliphatic rings in six new C(O)NHP(O)-based phosphoric triamide structures (analysed by X-ray crystallography) is investigated. Additionally the influence of steric and crystal packing effects is also studied by the analysis of Hirshfeld surfaces. The results are c...

A series of 3-Benzylchroman-4-ones were synthesized and screened for anticancer activity by MTT assay. The compounds were evaluated against two cancerous cell lines BT549 (human breast carcinoma), HeLa (human cervical carcinoma), and one noncancerous cell line vero (normal kidney epithelial cells). 3b was found to be the most active molecule agains...

Molecular characterization of neuraminidase (NA) gene of 25 influenza A(H3N2) virus isolates (2009-2013) archived at the Manipal Centre for Virus Research was carried out. The annual rate of amino acid substitutions in the N2 gene of influenza A(H3N2) virus isolates was 0.2-0.6%. Out of the 25 NA sequences analyzed, catalytic site mutations were ob...

Cancer therapeutic potential of thiadiazole hybrids incorporating pharmacologically active indole and coumarin moieties have not been explored much. In the current investigation, three new thiadiazole hybrids with spacers of varying lengths linking indole and thiadiazole units were synthesized and their structures were well-established using variou...

Laser-induced crystallization is emerging as a promising technique to crystallize biomolecules like amino acids and proteins. The use of external materials as nucleants and novel seeding methods open new paths for protein crystallization. We report here the results of experiments that explore the effect of nucleants on laser-based crystallization o...

The crystal structure of the title compound has been determined from X-ray diffraction studies. The compound crystallizes from methanol in the monoclinic system with space group P21/c with unit cell parameters: a= 10.647 (8), b=8.494 (6), c=16.743 (12) Å, β=92.731 (13)°, Z=4, V=1512.4(19)ų. The structure was determined by direct methods and refine...

The limited efficacy of marketed anticancer agents demands the design of novel target-specific hybrid molecules incorporating multiple bioactive pharmacores to combat cancer. In the present study, a one-pot simple and efficient T3P(®) mediated procedure for the preparation of twelve new 3-(substituted- [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazolo)-1H-...

Arsenic is a hazardous substance and exposure to inorganic arsenic leads to various vascular and carcinogenic diseases. Reduction of pentavalent arsenical to trivalency plays a critical role in its detoxification. We have earlier shown that human Cdc25B or Cdc25C protein tyrosine phosphatase catalyzes the reduction of inorganic arsenate to arsenite...

ic enzymes of metabolism, induction of oxidative stress, inhibition of DNA repair mechanisms and deregulation of cell proliferation. Despite its toxicity, arsenic has a long history of usage as chemotherapeutic agent. Today, drugs containing arsenic (and the related metalloid antimony) are used for treating acute promyelocytic leukemia and diseases...

Influenza, the most common infectious disease, poses a great threat to human health because of its highly contagious nature and fast transmissibility, often leading to high morbidity and mortality. Effective vaccination strategies may aid in the prevention and control of recurring epidemics and pandemics associated with this infectious disease. How...

Genetic analysis of neuraminidase gene sequences in 23 archived isolates of influenza A(H1N1)pdm09 virus, isolated during the 2009-2012 influenza seasons, was carried out to determine the genetic variability. Amino acid substitutions were observed at the rates of 0.3-0.7% per year. The catalytic site consisting of eight functional and 11 framework...

Small hybrid molecules with two or more structural pharmacores having different biological functions and distinct activity have gained a significant role in cancer drug development to combat various types of malignancies. The present study describes an efficient, clean and strategic synthesis of 12 new substituted quinoline–indole–oxadiazole hybrid...

A wide number of marketed drugs and drug candidates in cancer clinical development contain halogen substituents. The aim of the present study was to synthesize a series of halogen incorporated indole-coumarin hybrid schiff bases - N'-((2-(2-oxo-2H-chromen-3-yl)-1H-indol-3-yl)methylene)benzohydrazides and to investigate their apoptotic and anti-migr...

Influenza viruses are known to cause highly contagious respiratory illness in humans which can lead to potentially fatal outcomes. Influenza Neuraminidase (NA) inhibitors are the primary antivirals recommended for treating and preventing influenza (1). Studies have shown that residues that account for the catalytic function of NA are conserved amon...

Hybrid molecules have attracted attention for their improved biological activity, selectivity and lesser side effects profile, distinct from their individual components. In the quest for novel anticancer drug entities, three series of indole-coumarin hybrids - 3-(1-benzyl-1H-indol-2-yl)-2H-chromen-2-ones, 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carba...

Efflux is by far the most common means of arsenic detoxification. Another mechanism is methylation catalyzed by a family of As(III) S-adenosylmethionine (SAM) methyltransferases (MTs) enzymes designated ArsM in microbes or AS3MT in higher eukaryotes. The protein sequence of more than 5000 AS3MT/ArsM orthologues were deposited in the NCBI database,...

HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 c...

The structure based drug design has been limited by various factors that include protein crystallization, which is one of the most challenging tasks in this area. It has been proved unequivocally that X-ray crystallography is highly trusted technique for three dimensional structure determination of small-and macro-molecules. It has provided the def...

Methylation of the toxic metalloid arsenic is widespread in nature. Members of every kingdom have arsenic(III) S -adenosylmethionine (SAM) methyltransferase enzymes, which are termed ArsM in microbes and AS3MT in animals, including humans. Trivalent arsenic(III) is methylated up to three times to form methylarsenite [MAs(III)], dimethylarsenite [DM...

The ArsA ATPase is the catalytic subunit of the ArsAB As(III) efflux pump. It receives trivalent As(III) from the intracellular metallochaperone ArsD. The interaction of ArsA and ArsD allows for resistance to As(III) at environmental concentrations. A quadruple mutant in the arsD gene encoding a K2A/K37A/K62A/K104A ArsD is unable to interact with A...

Enzymatic methylation of arsenic is a detoxification process in microorganisms but in humans may activate the metalloid to more carcinogenic species. We describe the first structure of an As(III) S-adenosylmethionine methyltransferase by X-ray crystallography that reveals a novel As(III) binding domain. The structure of the methyltransferase from t...

Poster presented during IBS 2012 about ArsD modelling and docking studies

Arsenic and phosphorus are group 15 elements with similar chemical properties. Is it possible that arsenate could replace phosphate in some of the chemicals that are required for life? Phosphate esters are ubiquitous in biomolecules and are essential for life, from the sugar phosphates of intermediary metabolism to ATP to phospholipids to the phosp...

The ArsD metallochaperone delivers trivalent metalloids, As(III) or Sb(III), to the ArsA ATPase, the catalytic subunit of the ArsAB As(III) efflux pump. Transfer of As(III) increases the affinity of ArsA for As(III), allowing resistance to environmental arsenic concentrations. As(III) transfer is channelled from chaperone to ATPase, implying that A...

Arsenic, a toxic metalloid widely existing in the environment, causes a variety of health problems. The ars operon encoded by Escherichia coli plasmid R773 has arsD and arsA genes, where ArsA is an ATPase that is the catalytic subunit of the ArsAB As(III) extrusion pump, and ArsD is an arsenic chaperone for ArsA. ArsD transfers As(III) to ArsA and...

Arsenic is the most ubiquitous environmental toxin and carcinogen and consequently ranks first on the Environmental Protection Agency's Superfund Priority List of Hazardous Substances. It is introduced primarily from geochemical sources and is acted on biologically, creating an arsenic biogeocycle. A common biotransformation is methylation to monom...

Leishmania major aquaglyceroporin LmAQP1 allows adventitious passage of antimonite, an activated form of the drug Pentostam, which is used as the first line treatment for leishmaniasis. The extracellular C-loop of an aquaglyceroporin confers substrate specificity. Alteration of Glu125 to serine in the Plasmodium falciparum aquaglyceroporin PfAQP ha...

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Arsenic is a carcinogen that tops the Superfund list of hazardous chemicals. Bacterial resistance to arsenic is facilitated by ArsD, which delivers As(III) to the ArsA ATPase, the catalytic subunit of the ArsAB pump. Here we report the structure of the arsenic metallochaperone ArsD at 1.4 A and a model for its binding of metalloid. There are two Ar...

Rat glucose transporter isoform 1 or rGLUT1, which is expressed in neonatal heart and the epithelial cells that form the blood-brain barrier, facilitates uptake of the trivalent arsenicals arsenite as As(OH)₃ and methylarsenite as CH₃As(OH)₂. GLUT1 may be the major pathway for arsenic uptake into heart and brain, where the metalloid causes cardioto...

A number of eukaryotic enzymes that function as arsenate reductases are homologues of the catalytic domain of the human Cdc25 phosphatase. For example, the Leishmania major enzyme LmACR2 is both a phosphatase and an arsenate reductase, and its structure bears similarity to the structure of the catalytic domain of human Cdc25 phosphatase. These redu...

The ArsA ATPase belongs to the P-loop GTPase subgroup within the GTPase superfamily of proteins. Members of this subgroup have a deviant Walker A motif which contains a signature lysine that is predicted to make intermonomer contact with the bound nucleotides and to play a role in ATP hydrolysis. ArsA has two signature lysines located at positions...

The six-membered ring of the norbornene moiety in the title compound, C(18)H(18)N(4)O(4), is in a slightly distorted boat conformation, and the two five-membered rings within it adopt envelope conformations. The structure is stabilized by inter- and intramolecular N[bond]H...O hydrogen bonds.

The asymmetric unit of the title compound, C25H20N2O2, contains an enantiomeric pair of molecules, which are linked by N—H⋯O hydrogen bonds involving N—H and C=O groups of the pyrrole ring. In both mol­ecules, the central six-membered ring of the anthrone moiety adopts a boat conformation, the pyrrolidine ring adopts an envelope conformation and th...

The six-membered ring of the norbornene moiety in the title compound, C18H18N4O4, is in a slightly distorted boat conformation, and the two five-membered rings within it adopt envelope conformations. The structure is stabilized by inter- and intramolecular N—H⋯O hydrogen bonds.

In the title compound, C18H13N5O3S, both the five- and six-membered rings are planar. The phenyl ring attached to the sydnone ring is nearly perpendicular to both the sydnone ring [78.2 (1)°] and the thia­zole ring [80.1 (1)°]. The dihedral angle between the sydnone and thia­zole rings is 20.5 (1)°. The molecular packing in the crystal is stabilize...

The title compound, 2α,3β-24-tri­hydroxy­olean-12-en-28-oic acid, C30H48O5, is a stereoisomer of hyptatic acid A (2α,3β-24-tri­hydroxy­olean-12-en-28-oic methano­late). The central ring, which is flattened due to the presence of a C=C double bond, adopts a sofa conformation. All other six-membered rings adopt distorted chair conformations. The crys...

The title mol­ecule, C17H14O, contains p-methyl­benzyl­idene and 1-indanone moieties. The 1-indanone moiety is nearly planar and it forms a dihedral angle of 7.2 (2)° with the plane through the methyl­phenyl ring. The crystal structure is stabilized by C—H⋯O intermolecular interactions.

In the title compound, C14H9N3S, the triazole and benzo­thia­zole moieties are coplanar. The dihedral angle between the fused triazole–benzo­thia­zole fragment and the phenyl ring is 39.20 (5)°. The structure is stabilized by C—H⋯N intermolecular interactions.

The title compound, C22H36N2O, contains piperidine as a major constituent. The two piperidine rings attached to the phenyl ring are in chair conformations. The structure is stabilized by van der Waals forces as well as O—H⋯N intramolecular hydrogen bonds.

The title compound, C22H36N2O, contains piperidine as a major constituent. The two piperidine rings attached to the phenyl ring are in chair conformations. The structure is stabilized by van der Waals forces as well as O—H⋯N intramolecular hydrogen bonds.

The title compound, C22H36N2O, contains piperidine as a major constituent. The two piperidine rings attached to the phenyl ring are in chair conformations. The structure is stabilized by van der Waals forces as well as O-H . . .N intramolecular hydrogen bonds.

The title compound, C(23)H(15)Cl(2)NO(3), crystallizes with two independent molecules in the asymmetric unit. The chromanone moiety consists of a benzene ring fused with a six-membered heterocyclic ring which adopts a sofa conformation. The five-membered spiroisoxazoline ring is in an envelope conformation. The p-chlorophenyl rings bridged by the f...

The title compound, C23H15Cl2NO3, crystallizes with two independent molecules in the asymmetric unit. The chroman-one moiety consists of a benzene ring fused with a six-membered heterocyclic ring which adopts a sofa conformation. The five-membered spiroisoxazoline ring is in an envelope conformation. The p-chlorophenyl rings bridged by the five-mem...