ABSTRACT
Chikungunya virus is a growing human pathogen transmitted by mosquito bite. It causes fever, chills, nausea, vomiting, joint pain, headache, and swelling in the joints. Its replication and propagation depend on the protease activity of the Chikungunya virus-nsP2 protein, which cleaves the nsP1234 polyprotein replication complex into individual functional units. The N-terminal segment of papain is structurally identical with the Chikungunya virus-nsP2 protease. Hence, molecular dynamics simulations were performed to compare molecular mechanism of these proteases. The Chikungunya virus-snP2 protease shows more conformational changes and adopts an alternate conformation. However, N-terminal segment of these two proteases has identical active site scaffold with the conserved catalytic diad. Hence, some of the non-peptide inhibitors of papain were used for induced fit docking at the active site of the nsP2 to assess the binding mode. In addition, the peptides that connect different domains/protein in Chikungunya virus poly-protein were also subjected for docking. The overall results suggest that the active site scaffold is the same in both the proteases and a possibility exists to experimentally assess the efficacy of some of the papain inhibitors to inhibit the Chikungunya virus-nsP2.
Subject(s)
Chikungunya virus/enzymology , Cysteine Endopeptidases/chemistry , Papain/chemistry , Viral Proteins/chemistry , Amino Acid Sequence , Binding Sites , Catalytic Domain , Chikungunya Fever/pathology , Chikungunya Fever/virology , Cysteine Endopeptidases/metabolism , Cysteine Proteinase Inhibitors/chemistry , Cysteine Proteinase Inhibitors/metabolism , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Molecular Sequence Data , Papain/metabolism , Protein Binding , Protein Structure, Tertiary , Sequence Alignment , Structure-Activity Relationship , Thermodynamics , Viral Proteins/metabolismABSTRACT
The traditional knowledge of medicinal plants that are in use by the indigenous Jaintia tribes residing in few isolated pockets of North-East India is documented here. The present study was carried out through the personal discussion with the president of the Jaintia Indigenous Herbal Medicine Association, Dr.H.Carehome Pakyntein from Jowai, Meghalaya. The plants being used generation after generation by his family of herbalists to cure ailments like tuberculosis, cancer and diabetes were selected for the present study. In order to scientifically validate the use of these selected plants for the cure of selected diseases, phytochemical analyses, characterization and molecular docking studies of some of the selected compounds from these plants have been carried out. The compounds 2-hydroxy-4-methoxy- Benzaldehyde from methanolic extract of Strophanthus Wallichii and DL tetrahydropalmatine from Stephania Hernandifolia have been confirmed after determining their molecular structures, justifying the activity of these two plants against TB and cancer, respectively. The present study covers the potentials of some of the medicinal plants of North east India in curing common diseases due to which millions of people suffer and die. The presence of certain compounds in these plants related to the cure of the diseases deserves further studies.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Antitubercular Agents/chemistry , Benzaldehydes/chemistry , Berberine Alkaloids/chemistry , Hypoglycemic Agents/chemistry , Plant Extracts/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antitubercular Agents/isolation & purification , Benzaldehydes/isolation & purification , Berberine Alkaloids/isolation & purification , Humans , Hypoglycemic Agents/isolation & purification , India , Medicine, Traditional , Molecular Docking Simulation , Plants, Medicinal , ThermodynamicsABSTRACT
In the title compound, C34H32N2O7, the furan ring adopts a twist conformation and both the pyrrolidine rings adopt envelope conformations with O and C as flap atoms. The ß-lactam ring makes a dihedral angles of 80.20â (10)° with the furan ring, of 75.55â (10)° with the pyrrolidine ring, of 12.26â (10)° with the meth-oxy-phenyl ring and of 73.77â (13)° with the phenyl ring. The O atom attached to the ß-lactam ring deviates by 0.0385â (13)â Å from the ring plane. The mol-ecular conformation is stabilized by intra-molecular O-Hâ¯N and C-Hâ¯O hydrogen bonds. The packing of the crystal is stabilized by inter-molecular C-Hâ¯O hydrogen bonds, which form a chain running along the b axis.
ABSTRACT
In the title compound, [Fe(C5H5)(C32H24N3OS)], both the thia-zolidine ring and the pyrrolidine ring adopt an envelope conformation, with the S atom and the phenyl-bearing C atom, respectively, as the flaps. The thia-zolidine ring mean plane makes a dihedral angle of 59.08â (11)° with the pyrrolidine ring mean plane, which in turn makes a dihedral angle of 83.40â (10)° with the cyclo-pentane ring, indicating that the latter two rings are almost orthogonal to one another. In the crystal, a pair of C-Hâ¯O hydrogen bonds link the mol-ecules forming inversion dimers. The dimers are linked via π-π inter-actions [centroid-centroid distance = 3.7764â (10)â Å] involving the quinoxaline moieties forming chains propagating along [1-10].
ABSTRACT
In the title compound, [Fe(C5H5)(C32H23FN3OS)], both the thia-zolidine ring and the pyrrolidine ring adopt a twist conformation on the N-C(H) bridging bond. Their mean planes are inclined to one another by 10.05â (10)°, and they make dihedral angles of 82.09â (10) and 89.67â (11)°, respectively, with the cyclo-pentane ring. The F atom deviates by -0.0238â (2)â Å from the benzene ring to which it is attached. In the crystal, mol-ecules are linked by a pair of C-Hâ¯O hydrogen bonds, forming inversion dimers.
ABSTRACT
In the title compound, [Fe(C5H5)(C33H25BrN3O)], the fused four-ring system, 11H-indeno-[1,2-b]quinoxaline is essentially planar, with a maximum deviation of 0.087â (3)â Å from the least-squares plane of the attached benzene ring. The pyrrolidine rings adopt envelope conformation and make a dihedral angle of 51.76â (19)° with each other. The cyclopentadiene rings of the ferrocenyl moiety have an eclipsed conformation. The Br atom deviates by 0.0190â (9)â Å from the attached benzene ring. The mol-ecular structure features an intra-molecular C-Hâ¯N inter-action, which generates an S(8) ring motif. The crystal packing features C-Hâ¯O inter-actions, which generate R 2 (2)(18) centrosymmetric dimers, as well as C-Hâ¯π inter-actions.
ABSTRACT
In the title compound, C(38)H(31)ClN(2)O(4), the isoxazole ring adopts an envelope conformation with the N atom as the flap. The crystal packing is stabilized by C-Hâ¯O hydrogen bonds, forming chains running along the c-axis direction.
ABSTRACT
In the title compound, C33H29N3O5, the four-membered ring of the ß-lactam fragment is essentially planar (r.m.s. deviation = 0.0122â Å), with the carbonyl O atom displaced from this ring by 0.856â (9)â Å. The mean planes of the meth-oxy-phenyl and phenyl rings are inclined at dihedral angles 85.10â (7) and 21.56â (14)°, respectively, with respect to the mean plane of the four-membered ring. The pyrrolidine rings adopt envelope conformations with C atoms lying 0.535â (4) and 0.519â (4)â Å out of the planes formed by the remaining ring atoms. The furan ring also adopts an envelope conformation with a C atom 0.560â (3)â Å out of the plane formed by the remaining ring atoms. The nine-membered indene ring is almost planar (r.m.s. deviation = 0.0240â Å), with the carbonyl O atom displaced by 0.145â (3)â Å from this ring. The mol-ecular structure is stabilized by a strong intra-molecular O-Hâ¯N hydrogen bond and the crystal structure is consolidated by C-Hâ¯O hydrogen bonds.
ABSTRACT
In the title compound, C37H34N2O7, both pyrrolidine rings adopt envelope conformations. The ß-lactam ring is close to planar (r.m.s. deviation = 0.0395â Å) and makes a dihedral angle of 83.35â (15)° with the furan ring. The O atom attached to the ß-lactam ring deviates by 0.187â (2)â Å from the mean plane of the ring. The ß-lactam ring makes dihedral angles of 14.90â (15) and 27.72â (17)° with the meth-oxy-phenyl and phenyl rings, respectively. The crystal packing features C-Hâ¯O hydrogen bonds.
ABSTRACT
Medicinal plants and marine sources are important elements of indigenous medical systems worldwide. The natural drugs from medicinal plants and marine sources have received considerable interest in treatment of diabetes and inflammation. Based on literature, alpha glucosidase, aldose reductase and PTP1B enzymes were chosen as anti-diabetes targets and PLA(2) was chosen for the anti-inflammatory target. In our study, plant and bromophenols (BPs) inhibitors were screened using High Throughput Virtual screening (HTVS) followed by Induced Fit Docking (IFD) studies were carried out against diabetes and inflammation targets. The IFD result of natural inhibitors has showed favorable docking score, glide energy and hydrogen bonds interactions with the active site residues. Some of the natural inhibitors successively satisfied all the in silico parameters among the others and seem to be potent inhibitors against diabetes and inflammation.
