Parsharamulu Rayam - Academia.edu (original) (raw)
Papers by Parsharamulu Rayam
Analytical chemistry, an Indian journal, 2016
During the stress testing of linagliptin, one unknown degradation product (impurity I) on acidic ... more During the stress testing of linagliptin, one unknown degradation product (impurity I) on acidic conditions was detected in HPLC and subsequently isolated, identified, characterized by the spectral data (MS, MS/MS, 1D NMR, 2D NMR and infrared spectrum) and finally subjected for mechanism analysis. The degradation product (impurity I) and another process-related impurity (impurity II) of linagliptin were found to contain the structural alerts of N-Acylated aminoaryl and alkyl halide respectively, which were both potential genotoxic substances. Hence, a rapid and facile ultra-performance liquid chromatography method was developed for simultaneous determination of these two potential genotoxic impurities at ppm levels in linagliptin. The factors involved in the method development were discussed and this method was fully validated as per International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines, which proved
Medicinal Chemistry Research, Mar 3, 2016
Colon cancer is a widespread pathology with complex biochemical etiology based on a significant n... more Colon cancer is a widespread pathology with complex biochemical etiology based on a significant number of intracellular signaling pathways that play important roles in carcinogenesis, tumor proliferation and metastasis. These pathways function due to the action of key enzymes that can be used as targets for new anticancer drug development. Herein we report the synthesis and biological antiproliferative evaluation of a series of novel S-substituted 1H-3-R-5-mercapto-1,2,4-triazoles, on a colorectal cancer cell line, HT-29. Synthesized compounds were designed by docking based virtual screening (DBVS) of a previous constructed compound library against protein targets, known for their important role in colorectal cancer signaling: MEK1, ERK2, PDK1, VEGFR2. Among all synthesized structures, TZ55.7, which was retained as a possible PDK1 (phospholipid-dependent kinase 1) inhibitor, exhibited the most significant cytotoxic activity against HT-29 tumor cell line. The same compound alongside other two, TZ53.7 and TZ3a.7, led to a significant cell cycle arrest in both sub G0/G1 and G0/G1 phase. This study provides future perspectives for the development of new agents containing the 1,2,4-mercapto triazole scaffold with antiproliferative activities in colorectal cancer.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Transition metal complexes of 3-Methyl butanalthiosemicarbazone (MBTSC) derived from the condensa... more Transition metal complexes of 3-Methyl butanalthiosemicarbazone (MBTSC) derived from the condensation of 3-Methylbutaraldehyde with thiosemicarbazide are reported and characterized. Antibacterial activity of the ligand and its complexes were studied against selected bacteria. And their metal complexes of Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) their characterization are done by different analytical techniques, such as elemental analysis NMR ,FT-IR, ES-Mass.
ChemistrySelect, 2018
Pb(OAc)4 to assist N−N bond formation via dehydrogenative cyclization of hydrazide‐hydrazones to ... more Pb(OAc)4 to assist N−N bond formation via dehydrogenative cyclization of hydrazide‐hydrazones to generate the pyridazinones as bioactive molecules have been described. All the products were well characterized by various spectroscopic analyses. Furthermore, the structure of (E)‐3a,7‐diethyl‐6‐((thiophen‐2‐ylmethylene)amino)‐1,2,3a,4‐tetrahydro‐3‐oxa‐6,6a‐diazafluoranthen‐5(6H)‐one was unambiguously conformed by single crystal X‐ray analysis. The in vitro biological evaluation revealed that several of these compounds exhibited greater cytotoxic potency than that of doxorubicin drug. (E)‐N′‐(4‐chlorobenzylidene)‐2‐(1,8‐diethyl‐1,3,4,9‐tetrahydropyrano[3,4‐b]indol‐1‐yl)acetohydrazide exhibited most cytotoxic activity against both A549 and PC3 cancer cell lines with IC50 values of 1.77±0.08 and 1.88±0.33 μM, respectively.
Journal of Heterocyclic Chemistry, 2020
In the present study, we report design, synthesis and screening of new novel 5‐substituted‐2‐merc... more In the present study, we report design, synthesis and screening of new novel 5‐substituted‐2‐mercapto‐1,3,4‐oxadiazole analogues appended to oxaprozin for their in vitro anticancer and antibacterial activity. The synthesised compounds were characterized using various spectroscopic techniques. Furthermore, the structure of 5b (2‐(2‐[4,5‐diphenyloxazol‐2‐yl]ethyl)‐5‐(ethylthio)‐1,3,4‐oxadiazole) was unequivocally confirmed by X‐ray analysis. Among the series 5c (2‐(2‐[4,5‐diphenyloxazol‐2‐yl]ethyl)‐5‐(propylthio)‐1,3,4‐oxadiazole) showed most promising anticancer activity against A549 cancer cell line and all the reported analogues manifested satisfactory safety profiles against human normal cell line HEK293T. The products exhibited good antibacterial activity and among the tested 5j (2‐(2‐[4,5‐diphenyloxazol‐2‐yl]ethyl)‐5‐([4‐fluorobenzyl]thio)‐1,3,4‐oxadiazole) exhibited most potent.
Journal of Heterocyclic Chemistry, 2018
A new hybrid polydentate template comprising distinctive pharmacophoric groups, namely, ibuprofen... more A new hybrid polydentate template comprising distinctive pharmacophoric groups, namely, ibuprofen, 1,3,4-oxadiazole, and 1,2,3-triazole linked through a thioether bridge was achieved by one-pot synthesis by exploring multicomponent Cu-catalyzed "click chemistry" approach. The target structures were characterized by NMR, IR, and LC-Mass. The X-ray analysis of 2-(1-(4-isobutylphenyl)ethyl)-5-(((1-(3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-1,3,4-oxadiazole (8a) confirmed the assigned structure. The in vitro antibacterial and anticancer activity of these compounds revealed that 2-(1-(4-isobutylphenyl) ethyl)-5-(((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)thio)-1,3,4-oxadiazole (8b) demonstrated more potent antibacterial activity against Gram-negative strains (Escherichia coli and Pseudomonas aeruginosa) and 2-(((1-(2,4-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5-(1-(4 isobutylphenyl)ethyl)-1,3,4-oxadiazole (8e) exhibited anticancer activity with IC 50 of 27.50 and 31.03 μg/mL against HeLa and MCF-7 cell lines, respectively.
ChemistrySelect, 2017
A series of regioisomeric (2,5-dimethoxybenzoic acid, veratric acid) analogues were prepared by s... more A series of regioisomeric (2,5-dimethoxybenzoic acid, veratric acid) analogues were prepared by swapping the carboxylic motif to its oxadiazole bioisostere and have been screened for in vitro anticancer studies by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay. All of them were well characterized by spectroscopic techniques. Among the screened compounds, 9 i (2-(2,5-dimethoxyphenyl)-5-(5-phenylthiophen-2-yl)-1,3,4-oxadiazole) demonstrated superior activity against MDA231 cells. Products 9 i displayed excellent activity against DU145, HCT15 and 10 i (2-(3,4dimethoxyphenyl)-5-(5-phenylthiophen-2-yl)-1,3,4-oxadiazole) against MDA231 cells. Structure of 10 c (2-(3,4-dimethoxyphenyl)-5-(2,4,6-trimethoxyphenyl)-1,3,4-oxadiazole) was further authenticated through single crystal X-ray diffraction. Analogue 9 i have come out to be the best anticancer and antimycobacterial agent.
![Research paper thumbnail of Synthesis of Novel 2-Butyl-1H-Benzo [4, 5] Imidazo [1, 2-A] Imidazo [4, 5-E] Pyridine-5-Carbonitrile Derivatives and Evaluation of Their Anticancer Activity](https://attachments.academia-assets.com/115108089/thumbnails/1.jpg)
](Oriental Journal of Chemistry, 2016
A series of new 2-butyl-1H-benzo[4,5]imidazo[1,2-a]imidazo[4,5-e]pyridine-5-carbonitrile derivati... more A series of new 2-butyl-1H-benzo[4,5]imidazo[1,2-a]imidazo[4,5-e]pyridine-5-carbonitrile derivatives were synthesized by the self cyclisation of (E)-2-(1H-benzo[d]imidazol-2-yl)-3-(2-butyl-4-chloro-1H-imidazol-5-yl)acrylonitrile in the presence of piperidine as catalyst, which in turn were prepared by the condensation of substituted N-alkyl 2-butyl-4-chloro-1H-imidazole-5-carbaldehydes with 2-cyanomethylbenzimidazole in the presence of catalytic amount of L-proline in ethanol or by using piperidine as a base. Newly synthesized compounds which incorporate a variety of N-substituent moieties were characterized by spectral data and screened for anticancer activity against MCF-7 breast cancer cell line. The results showed that compounds 3b, 3a and 4b possess significant anti proliferative activity with IC 50 values 26.59 and 27.98, 36.95 µM respectively.
Medicinal Chemistry Research, 2016
Colon cancer is a widespread pathology with complex biochemical etiology based on a significant n... more Colon cancer is a widespread pathology with complex biochemical etiology based on a significant number of intracellular signaling pathways that play important roles in carcinogenesis, tumor proliferation and metastasis. These pathways function due to the action of key enzymes that can be used as targets for new anticancer drug development. Herein we report the synthesis and biological antiproliferative evaluation of a series of novel S-substituted 1H-3-R-5-mercapto-1,2,4-triazoles, on a colorectal cancer cell line, HT-29. Synthesized compounds were designed by docking based virtual screening (DBVS) of a previous constructed compound library against protein targets, known for their important role in colorectal cancer signaling: MEK1, ERK2, PDK1, VEGFR2. Among all synthesized structures, TZ55.7, which was retained as a possible PDK1 (phospholipid-dependent kinase 1) inhibitor, exhibited the most significant cytotoxic activity against HT-29 tumor cell line. The same compound alongside other two, TZ53.7 and TZ3a.7, led to a significant cell cycle arrest in both sub G0/G1 and G0/G1 phase. This study provides future perspectives for the development of new agents containing the 1,2,4-mercapto triazole scaffold with antiproliferative activities in colorectal cancer.
Bioorganic & Medicinal Chemistry Letters, 2015
Bioorganic Medicinal Chemistry Letters, Feb 20, 2015
A series of 2,5-disubstituted-1,3,4-thiadiazole derivatives 5a-5l, 7a-7e and 9 have been synthesi... more A series of 2,5-disubstituted-1,3,4-thiadiazole derivatives 5a-5l, 7a-7e and 9 have been synthesised and screened for in vitro antimycobacterial activity against Mycobacterium smegmatis MC-155. In addition these compounds have also been screened for cytotoxic activity against cancer cell lines HT-29, MDA-MB-231 by MTT colorimetric assay. The compounds are well characterized by spectral analysis viz. (1)H NMR, (13)C NMR, FT-IR, mass and HRMS. Screening results indicate that compounds 5g, 7a possess good antitubercular activity with MIC value 65.74 and 40.86, respectively, compounds 5g, 7a, 7b, 7d, 7e and 9 displayed promising cytotoxic activity against the cell lines tested. 5g and 7a stand out to be potent antimycobacterial and anticancer agents among the tested series. Further the title compounds were also tested on human normal cells HEK293T and are found to be safer with lesser cytotoxicity. It is interesting to observe that compound 5g has come out to be safer, potent anticancer and antimycobacterial agent.
Analytical chemistry, an Indian journal, 2016
During the stress testing of linagliptin, one unknown degradation product (impurity I) on acidic ... more During the stress testing of linagliptin, one unknown degradation product (impurity I) on acidic conditions was detected in HPLC and subsequently isolated, identified, characterized by the spectral data (MS, MS/MS, 1D NMR, 2D NMR and infrared spectrum) and finally subjected for mechanism analysis. The degradation product (impurity I) and another process-related impurity (impurity II) of linagliptin were found to contain the structural alerts of N-Acylated aminoaryl and alkyl halide respectively, which were both potential genotoxic substances. Hence, a rapid and facile ultra-performance liquid chromatography method was developed for simultaneous determination of these two potential genotoxic impurities at ppm levels in linagliptin. The factors involved in the method development were discussed and this method was fully validated as per International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines, which proved
Medicinal Chemistry Research, Mar 3, 2016
Colon cancer is a widespread pathology with complex biochemical etiology based on a significant n... more Colon cancer is a widespread pathology with complex biochemical etiology based on a significant number of intracellular signaling pathways that play important roles in carcinogenesis, tumor proliferation and metastasis. These pathways function due to the action of key enzymes that can be used as targets for new anticancer drug development. Herein we report the synthesis and biological antiproliferative evaluation of a series of novel S-substituted 1H-3-R-5-mercapto-1,2,4-triazoles, on a colorectal cancer cell line, HT-29. Synthesized compounds were designed by docking based virtual screening (DBVS) of a previous constructed compound library against protein targets, known for their important role in colorectal cancer signaling: MEK1, ERK2, PDK1, VEGFR2. Among all synthesized structures, TZ55.7, which was retained as a possible PDK1 (phospholipid-dependent kinase 1) inhibitor, exhibited the most significant cytotoxic activity against HT-29 tumor cell line. The same compound alongside other two, TZ53.7 and TZ3a.7, led to a significant cell cycle arrest in both sub G0/G1 and G0/G1 phase. This study provides future perspectives for the development of new agents containing the 1,2,4-mercapto triazole scaffold with antiproliferative activities in colorectal cancer.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Transition metal complexes of 3-Methyl butanalthiosemicarbazone (MBTSC) derived from the condensa... more Transition metal complexes of 3-Methyl butanalthiosemicarbazone (MBTSC) derived from the condensation of 3-Methylbutaraldehyde with thiosemicarbazide are reported and characterized. Antibacterial activity of the ligand and its complexes were studied against selected bacteria. And their metal complexes of Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) their characterization are done by different analytical techniques, such as elemental analysis NMR ,FT-IR, ES-Mass.
ChemistrySelect, 2018
Pb(OAc)4 to assist N−N bond formation via dehydrogenative cyclization of hydrazide‐hydrazones to ... more Pb(OAc)4 to assist N−N bond formation via dehydrogenative cyclization of hydrazide‐hydrazones to generate the pyridazinones as bioactive molecules have been described. All the products were well characterized by various spectroscopic analyses. Furthermore, the structure of (E)‐3a,7‐diethyl‐6‐((thiophen‐2‐ylmethylene)amino)‐1,2,3a,4‐tetrahydro‐3‐oxa‐6,6a‐diazafluoranthen‐5(6H)‐one was unambiguously conformed by single crystal X‐ray analysis. The in vitro biological evaluation revealed that several of these compounds exhibited greater cytotoxic potency than that of doxorubicin drug. (E)‐N′‐(4‐chlorobenzylidene)‐2‐(1,8‐diethyl‐1,3,4,9‐tetrahydropyrano[3,4‐b]indol‐1‐yl)acetohydrazide exhibited most cytotoxic activity against both A549 and PC3 cancer cell lines with IC50 values of 1.77±0.08 and 1.88±0.33 μM, respectively.
Journal of Heterocyclic Chemistry, 2020
In the present study, we report design, synthesis and screening of new novel 5‐substituted‐2‐merc... more In the present study, we report design, synthesis and screening of new novel 5‐substituted‐2‐mercapto‐1,3,4‐oxadiazole analogues appended to oxaprozin for their in vitro anticancer and antibacterial activity. The synthesised compounds were characterized using various spectroscopic techniques. Furthermore, the structure of 5b (2‐(2‐[4,5‐diphenyloxazol‐2‐yl]ethyl)‐5‐(ethylthio)‐1,3,4‐oxadiazole) was unequivocally confirmed by X‐ray analysis. Among the series 5c (2‐(2‐[4,5‐diphenyloxazol‐2‐yl]ethyl)‐5‐(propylthio)‐1,3,4‐oxadiazole) showed most promising anticancer activity against A549 cancer cell line and all the reported analogues manifested satisfactory safety profiles against human normal cell line HEK293T. The products exhibited good antibacterial activity and among the tested 5j (2‐(2‐[4,5‐diphenyloxazol‐2‐yl]ethyl)‐5‐([4‐fluorobenzyl]thio)‐1,3,4‐oxadiazole) exhibited most potent.
Journal of Heterocyclic Chemistry, 2018
A new hybrid polydentate template comprising distinctive pharmacophoric groups, namely, ibuprofen... more A new hybrid polydentate template comprising distinctive pharmacophoric groups, namely, ibuprofen, 1,3,4-oxadiazole, and 1,2,3-triazole linked through a thioether bridge was achieved by one-pot synthesis by exploring multicomponent Cu-catalyzed "click chemistry" approach. The target structures were characterized by NMR, IR, and LC-Mass. The X-ray analysis of 2-(1-(4-isobutylphenyl)ethyl)-5-(((1-(3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-1,3,4-oxadiazole (8a) confirmed the assigned structure. The in vitro antibacterial and anticancer activity of these compounds revealed that 2-(1-(4-isobutylphenyl) ethyl)-5-(((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)thio)-1,3,4-oxadiazole (8b) demonstrated more potent antibacterial activity against Gram-negative strains (Escherichia coli and Pseudomonas aeruginosa) and 2-(((1-(2,4-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5-(1-(4 isobutylphenyl)ethyl)-1,3,4-oxadiazole (8e) exhibited anticancer activity with IC 50 of 27.50 and 31.03 μg/mL against HeLa and MCF-7 cell lines, respectively.
ChemistrySelect, 2017
A series of regioisomeric (2,5-dimethoxybenzoic acid, veratric acid) analogues were prepared by s... more A series of regioisomeric (2,5-dimethoxybenzoic acid, veratric acid) analogues were prepared by swapping the carboxylic motif to its oxadiazole bioisostere and have been screened for in vitro anticancer studies by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay. All of them were well characterized by spectroscopic techniques. Among the screened compounds, 9 i (2-(2,5-dimethoxyphenyl)-5-(5-phenylthiophen-2-yl)-1,3,4-oxadiazole) demonstrated superior activity against MDA231 cells. Products 9 i displayed excellent activity against DU145, HCT15 and 10 i (2-(3,4dimethoxyphenyl)-5-(5-phenylthiophen-2-yl)-1,3,4-oxadiazole) against MDA231 cells. Structure of 10 c (2-(3,4-dimethoxyphenyl)-5-(2,4,6-trimethoxyphenyl)-1,3,4-oxadiazole) was further authenticated through single crystal X-ray diffraction. Analogue 9 i have come out to be the best anticancer and antimycobacterial agent.
Oriental Journal of Chemistry, 2016
A series of new 2-butyl-1H-benzo[4,5]imidazo[1,2-a]imidazo[4,5-e]pyridine-5-carbonitrile derivati... more A series of new 2-butyl-1H-benzo[4,5]imidazo[1,2-a]imidazo[4,5-e]pyridine-5-carbonitrile derivatives were synthesized by the self cyclisation of (E)-2-(1H-benzo[d]imidazol-2-yl)-3-(2-butyl-4-chloro-1H-imidazol-5-yl)acrylonitrile in the presence of piperidine as catalyst, which in turn were prepared by the condensation of substituted N-alkyl 2-butyl-4-chloro-1H-imidazole-5-carbaldehydes with 2-cyanomethylbenzimidazole in the presence of catalytic amount of L-proline in ethanol or by using piperidine as a base. Newly synthesized compounds which incorporate a variety of N-substituent moieties were characterized by spectral data and screened for anticancer activity against MCF-7 breast cancer cell line. The results showed that compounds 3b, 3a and 4b possess significant anti proliferative activity with IC 50 values 26.59 and 27.98, 36.95 µM respectively.
Medicinal Chemistry Research, 2016
Colon cancer is a widespread pathology with complex biochemical etiology based on a significant n... more Colon cancer is a widespread pathology with complex biochemical etiology based on a significant number of intracellular signaling pathways that play important roles in carcinogenesis, tumor proliferation and metastasis. These pathways function due to the action of key enzymes that can be used as targets for new anticancer drug development. Herein we report the synthesis and biological antiproliferative evaluation of a series of novel S-substituted 1H-3-R-5-mercapto-1,2,4-triazoles, on a colorectal cancer cell line, HT-29. Synthesized compounds were designed by docking based virtual screening (DBVS) of a previous constructed compound library against protein targets, known for their important role in colorectal cancer signaling: MEK1, ERK2, PDK1, VEGFR2. Among all synthesized structures, TZ55.7, which was retained as a possible PDK1 (phospholipid-dependent kinase 1) inhibitor, exhibited the most significant cytotoxic activity against HT-29 tumor cell line. The same compound alongside other two, TZ53.7 and TZ3a.7, led to a significant cell cycle arrest in both sub G0/G1 and G0/G1 phase. This study provides future perspectives for the development of new agents containing the 1,2,4-mercapto triazole scaffold with antiproliferative activities in colorectal cancer.
Bioorganic & Medicinal Chemistry Letters, 2015
Bioorganic Medicinal Chemistry Letters, Feb 20, 2015
A series of 2,5-disubstituted-1,3,4-thiadiazole derivatives 5a-5l, 7a-7e and 9 have been synthesi... more A series of 2,5-disubstituted-1,3,4-thiadiazole derivatives 5a-5l, 7a-7e and 9 have been synthesised and screened for in vitro antimycobacterial activity against Mycobacterium smegmatis MC-155. In addition these compounds have also been screened for cytotoxic activity against cancer cell lines HT-29, MDA-MB-231 by MTT colorimetric assay. The compounds are well characterized by spectral analysis viz. (1)H NMR, (13)C NMR, FT-IR, mass and HRMS. Screening results indicate that compounds 5g, 7a possess good antitubercular activity with MIC value 65.74 and 40.86, respectively, compounds 5g, 7a, 7b, 7d, 7e and 9 displayed promising cytotoxic activity against the cell lines tested. 5g and 7a stand out to be potent antimycobacterial and anticancer agents among the tested series. Further the title compounds were also tested on human normal cells HEK293T and are found to be safer with lesser cytotoxicity. It is interesting to observe that compound 5g has come out to be safer, potent anticancer and antimycobacterial agent.