Papers by Achaiah Garlapati
European journal of medicinal chemistry, May 1, 2011
A novel class of 4-aryl/heteroaryl-2,6-dimethyl-3,5-bis-N-(phenyl/substituted phenyl)-carbamoyl-1... more A novel class of 4-aryl/heteroaryl-2,6-dimethyl-3,5-bis-N-(phenyl/substituted phenyl)-carbamoyl-1,4-dihydropyridines has been synthesized by simple, economical and eco-friendly, modified Hantzsch condensation reaction making use of N-arylacetoacetamides, aryl or heteroaryl aldehydes and ammonium acetate. The newly synthesized compounds were characterized by their spectral (IR, 1H NMR, Mass), elemental analyses data and evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv ATCC 27294 and antibacterial activity against different Gram +ve and Gram -ve bacteria. The preliminary screening results revealed that some of the compounds possess promising antimicrobial activity. Amongst the new series of compounds, 6m containing pyrrolyl and 4-methylphenyl groups and 6r possessing 2-pyridyl and 2-methylphenyl groups were found to exhibit a significant antitubercular activity (MIC=12.5-25 μg/mL) in comparison with the first line drug pyrazinamide.
Pharmaceutical Chemistry Journal, Apr 1, 2018
Journal of Biomolecular Structure and Dynamics
Anti-Cancer Agents in Medicinal Chemistry
Background: PIM (Proviral Integration site for Moloney Murine Leukemia virus) kinases are members... more Background: PIM (Proviral Integration site for Moloney Murine Leukemia virus) kinases are members of the class of kinase family serine/ threonine kinases, which play a crucial role in cancer development. As there is no drug in the market against PIM-1, kinase has transpired as a budding and captivating target for discovering new anticancer agents targeting PIM-1 kinase. Aim: The current research pondered the development of new PIM-1 kinase inhibitors by applying a ligand-based and structure-based drug discovery approach involving 3D QSAR, molecular docking, and dynamics simulation. Method: In this study, association allying the structural properties and biological activity was undertaken using 3D-QSAR analysis. The 3D-QSAR model was generated with the help of 35 compounds from which the best model manifested an appreciated cross-validation coefficient (q2) of 0.8866 and conventional correlation coefficient (r2) of 0.9298, respectively and predicted correlation coefficient (r2 pred) ...
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2022
Cytosolic PIM kinases are the members of serine/ threonine family play a crucial role in the canc... more Cytosolic PIM kinases are the members of serine/ threonine family play a crucial role in the cancer progression and development. Overexpression of PIM kinases is observed in various types of cancers including prostate, hematological, pancreatic, breast carcinoma and likewise. PIM kinases have now been considered as limelight target for the discovery of new molecules as novel anticancer agents as no drug is in market targeting PIM kinases. In the last two decades, numerous PIM kinase inhibitors have been developed and few of them were in clinical trial phases but could not pass the pipeline of the clinical trials. The present comprehensive review intends to cover biological and the structural aspects of PIM kinases and also medicinal chemistry of PIM inhibitors developed in recent years.
Indian Journal of Pharmaceutical Sciences, 1991
A condensation of four different 3-formychromones with 2-methyl/phenyl-3-amino-4 (3H)-quinazolino... more A condensation of four different 3-formychromones with 2-methyl/phenyl-3-amino-4 (3H)-quinazolinone and their dibromo analogs has resulted in twelve new compounds which have been characterized as their respective 3-[N-(4-oxo-2-methyl/phenyl-3-quinazolinyl) formimidoyl] chromones, based on their spectro-analytical properties. They have been found to exhibit promising antibacterial and antifungal properties.
Indian Journal of Chemistry Section B-organic Chemistry Including Medicinal Chemistry, 1988
![Research paper thumbnail of Design, Synthesis and Evaluation of New 2, 6-Dihydroimidazo[1, 2-c]Pyrimido[5, 4-e]-Pyrimidine-5(3H)-thiones as Possible Antihistaminic/Antiasthmatic Agents§](https://attachments.academia-assets.com/114300832/thumbnails/1.jpg)
Indian Journal of Pharmaceutical Sciences, 2014
A series of new 10-(alkylamino)-8-methyl-2, 6-dihydroimidazo[1, 2-c]pyrimido[5, 4-e]pyrimidine-5(... more A series of new 10-(alkylamino)-8-methyl-2, 6-dihydroimidazo[1, 2-c]pyrimido[5, 4-e]pyrimidine-5(3H)-thiones (4a-g) were subjected to molecular property prediction (drug-likeness, lipophilicity and solubility parameters) using Osiris Property Explorer, ALOGPS 2.1, Molinspiration and ACD/Chemsketch 12.0 software programmes. The calculated drug-related properties of the designed molecules were similar to those found in most marketed drugs. Amongst the proposed analogues, four promising candidates were chosen (4a-d) for synthesis on the basis of Lipinski's ‘Rule of Five’ and drug-likeness scores. The significant biological activity of the test compounds in two in vitro modes (isolated guinea pig tracheal chain preparation, isolated guinea pig ileum) supports the promise and accuracy of the prediction. Among them, 4a was the most potent antihistaminic (IC50 value of 30.2 μM; standard, chlorpheniramine maleate showed an IC50 of 14.1 μM).
Compounds containing pyrazolylurea group are known to possess potent anti-inflammatory activity b... more Compounds containing pyrazolylurea group are known to possess potent anti-inflammatory activity by inhibiting cell signalling system. One of the potent compounds has demonstrated CNS related adverse effects in human studies which has further intensified the quest to search potent but safe antiinflammatory agents. In the present study, an attempt has been made to modify the urea group into α-ketoamide group. The synthesis involved the coupling of 5-aminopyrazole with substituted α-keto acids in presence of a coupling agent to afford the desired compounds and the structures of the synthesized compounds have been confirmed by spectral data. Compounds have been screened for antiinflammatory activity by carrageenan induced rat paw method. Compounds 6c, 6e and 6f demonstrate greater than 70% paw oedema protection when compared with indomethacin. The preliminary structure activity relationship suggests that the electron withdrawing groups are essential for potent antiinflammatory activity ...
Asian Journal of Organic & Medicinal Chemistry, 2020
Substituted 2-(2-(4-aryloxybenzylidene)hydrazinyl)benzothiazole/benzoxazoles series were designed... more Substituted 2-(2-(4-aryloxybenzylidene)hydrazinyl)benzothiazole/benzoxazoles series were designed through molecular hybridization and synthesized in condensation reaction of hydrazinylbenzothiazole/ benzoxazole with substituted aryloxy benzaldehydes. All the synthesized compounds were assigned structure based on spectral data and were evaluated for antimycobacterial activity. Among both benzothiazole and benzoxazole derivatives, the compounds 8f and 9e were found to show most potent antitubercular activity with MIC value of 0.89 and 0.92 μM which are on a par with those of standard antitubercular drugs. In order to know the binding interactions of all the compounds were docked within the mycobacterial pantothenate synthetase, which showed interactions with Asp88, Arg200, Ser196, Asn199, Met 195 and Lys 160 of pantothenate synthetase.
International Journal of Pharmaceutical Sciences and Nanotechnology, 2009
Benzoxazoles and Oxazolo-[4,5-b]pyridines have been reported as potent anti-fungal agents. 3D QS... more Benzoxazoles and Oxazolo-[4,5-b]pyridines have been reported as potent anti-fungal agents. 3D QSAR tools including CoMFA and CoMSIA have been known to be a promising approaches is to correlate structures and activity which further enable the medicinal chemists to design more potent molecules thus curtailing the cost and time in drug research. CoMFA and CoMSIA studies have been carried out on 31 molecules of benzoxazole and oxazolopyridines in order to determine the structural properties required for effective antifungal activity. 26 compounds were evaluated for establishing QSAR model, which was then validated by predicting the activities of five test set molecules. All the molecules were aligned by SYBYL database alignment which led to a best model with q2 value of 0.835, r2=0.976 and r2pred=0.773. This model was further employed to derive CoMSIA models, a best model with steric, electrostatic, hydrophobic and hydrogen bond acceptor indices exhibited q2 = 0.812, r2=0.971 and r2pre...
Mini reviews in medicinal chemistry, Jan 7, 2017
A series of amides possessing phenoxy/benzyloxy/pyridinyl groups has been synthesized by benzoyla... more A series of amides possessing phenoxy/benzyloxy/pyridinyl groups has been synthesized by benzoylation of respective amines in presence of base with moderate to encouraging yields. Upon confirmation of structure, compounds were subjected for p38 kinase inhibitory, anti-inflammatory, antimicrobial and antitubercular activities. Antiinflammatory activity was determined using carageenan induced rat paw edema model while p38 kinase inhibitory activity was studied using ELISA method and serial dilution method was employed to determine MICs. Two compounds 4g and 4n showed over 30% p38 kinase inhibitory activity at 10 μM and best antiinflammatory activity was found for compounds 4g, 4i, 4n and 4o which exhibited to reduce paw edema over 70%. Compound 4b observed to be most potent against gram +ve organisms with MIC value of 1.6 μG/mL and compound 4u displayed potent antibacterial activity against gram negative organisms. Most encourging antitubercular activity was noticed for compounds 4u, ...
Archiv der Pharmazie, 2010
A series of twenty new 4‐substituted‐2,6‐dimethyl‐3,5‐bis‐N‐(heteroaryl)‐carbamoyl‐1,4‐dihydropyr... more A series of twenty new 4‐substituted‐2,6‐dimethyl‐3,5‐bis‐N‐(heteroaryl)‐carbamoyl‐1,4‐dihydropyridines have been prepared from a three‐component one‐pot condensation reaction of N‐heteroaryl acetoacetamide, an aromatic/heteroaromatic aldehyde, and ammonium acetate under four different experimental conditions. Except for the conventional method, all the experimental conditions were simple, eco‐friendly, economical, and the reactions were rapid and high‐yielding. The methods employed have been compared in terms of yields, cost, and simplicity. The synthesized compounds were characterized by different spectroscopic techniques and evaluated for their in‐vitro anticancer, antibacterial, and antitubercular activities. Amongst the compounds tested, compound 25 exhibited the highest anticancer activity while compounds 14 and 18 exhibited significant antibacterial and antitubercular activities.
Journal of Computer-Aided Molecular Design, 2007
Journal of diabetes & metabolism, Jun 5, 2018
International Journal of Pharmaceutical Investigation
Medicinal Chemistry, 2017
International Journal of Sciences: Basic and Applied Research, 2016
1,4-dihydropyridine derivatives represent one of the important classes of compounds possessing a ... more 1,4-dihydropyridine derivatives represent one of the important classes of compounds possessing a wide variety of biological activities including anticancer activity. In the present study, (4-Alkyl/Aryl-1-substituted 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxilicacid, 3,5-bis [2(aminothioxomethyl)hydrazides]) (6 a-l) were synthesized by the reaction of 4-alkyl/aryl-3,5-dicarboalkoxy-2,6-dimethyl-1,4-dihydropyridines (4 a-l) with thisemicarbazide and evaluated for their anti-cancer properties. All the synthesized compounds were characterized by IR, NMR and Mass spectra and were screened to evaluating for anticancer activity against three cell lines (MCF-7, HeLa and Hep G 2 ) by using MTT assay method. The results showed that compounds 6j and 6l showed significant cytotoxicity with IC 50 values ranging from 56µM - 74µM.
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Papers by Achaiah Garlapati