Rational drug discovery and development require a streamlined interdisciplinary effort from researchers working in a specialized area. From active collaboration, the drug discovery process can be and has been significantly shortened by addressing bottlenecks in drug discovery (off-target effects, polypharmacology, and chemoresistance). Our research focuses on some unaddressed questions that could contribute to chemotherapy.
Establishing the bioactivity of a lead molecule (of any origin) from an in vitro study is the start of a long journey in the drug discovery pipeline. The pharmacological effect of the lead molecule observed in vitro may not directly correlate with the in vivo results due to the molecule's physicochemical properties, bio-pharmacokinetics, or structural mimicry. Here, we try to design suitable study models (in silico, in vitro, and/or in vivo) that can progressively help develop a reliable formulation.
The following are the areas and related publications we presently focus on:
Drug Delivery of Poorly-soluble Phytochemicals
- Haloi P, Siva Lokesh B, Chawla S, Konkimalla VB. Formulation of a dual drug-loaded nanoparticulate co-delivery hydrogel system and its validation in rheumatoid arthritis animal model. Drug Delivery. 2023; 30(1): 2184307.
- Haloi P, Chawla S and Konkimalla VB. Thermosensitive smart hydrogel of PEITC ameliorates the therapeutic efficacy in Rheumatoid arthritis. European Journal of Pharmaceutical Sciences. 2023: 181: 106367.
- Siva Lokesh B, Haloi P, Konkimalla VB. Fabrication and Optimization of BSA-PEG-loaded Phenethyl Isothiocyanate (PEITC) nanoparticles using Box-Behnken Design for potential application in subcutaneous infection conditions. Journal of Drug Delivery Science and Technology. 2022; 104101.
- Mohanty S, Sahoo AK, Konkimalla VB, Pal A, and Si SC. Naringin in Combination with Isothiocyanates as Liposomal Formulations Potentiates the Anti-inflammatory Activity in Different Acute and Chronic Animal Models of Rheumatoid Arthritis. ACS Omega. 2020; 5(43): 28319–28332.
Interdisciplinary approaches in the development of cancer therapeutics
- Shinde Y, Patil R, Konkimalla VB, Merugu SB, Mokashi V, Harihar S, Marrot J, Butcher RJ, Salunke-Gawali S. Keto-enol tautomerism of hydroxynaphthoquinoneoxime ligands-Copper complexes and topoisomerase inhibition activity. Journal of Molecular Structure. 2022; 1262: 133081
- Dash TK, Konkimalla VB. Selection of P-Glycoprotein Inhibitor and Formulation of Combinational Nanoformulation Containing Selected Agent Curcumin and DOX for Reversal of Resistance in K562 Cells. Pharm Res. 2017;34(8):1741-1750.
- Dash TK, Konkimalla VB. Selection and optimization of nano-formulation of P-glycoprotein inhibitor for reversal of doxorubicin resistance in COLO205 cells. J Pharm Pharmacol. 2017;69(7):834-843.
- Dash TK, Konkimalla VB. Comparative Study of Different Nano-Formulations of Curcumin for Reversal of Doxorubicin Resistance in K562R Cells. Pharmaceutical Research. 2017;34(2):279-289.
- Dash TK, Konkimalla VB. Formulation and Optimization of Doxorubicin and Biochanin A Combinational Liposomes for Reversal of Chemoresistance. AAPS PharmSciTech. 2017;18(4):1116-1124.
- Patil R, Bhand S, Konkimalla VB, Banerjee P, Ugale B, Chadar D, Saha SK, Praharaj PP, Nagaraja, CM, Chakrovarty D. Molecular association of 2-(n-alkylamino)-1, 4-naphthoquinone derivatives: Electrochemical, DFT studies and antiproliferative activity against leukemia cell lines. Journal of Molecular Structure. 2016; 1125,272-281.
- Pal S, Konkimalla VB*, Kathwate L, Rao SS, Gejji SP, Puranik V, Weyhermueller T, and Salunke-Gawali S. Targeting chemorefractory COLO205 (BRAF-V600E) cell lines using substituted benzo[a]phenoxazines. RSC Adv. 2015; 5: 82549-82563.
Understanding cellular response to different ligands deriving its implications
- Pal S, Salunke-Gawali S, Konkimalla VB. Induction of Autophagic Cell Death In Apoptosis-Resistant Pancreatic Cancer Cells Using Benzo [α] Phenoxazines Derivatives, 10-Methyl-Benzo [α] Phenoxazine-5-One And Benzo [α] Phenoxazine-5-One. Anti-cancer agents in medicinal chemistry. 2016,
- Pal S and Konkimalla VB. Sulforaphane regulates phenotypic and functional switching of both induced and spontaneously differentiating human monocytes. International Immunopharmacology. 2016; 35:85-98.
- Pal S and Konkimalla VB. Data on sulforaphane treatment mediated suppression of autoreactive, inflammatory M1 macrophages. Data Brief. 2016 Apr 25;7:1560-4. – Supplementary data of publication from International Immunopharmacology
- Pal S and Konkimalla VB. Hormetic potential of Sulforaphane (SFN) in switching cells' fate towards survival or death. Mini Rev Med Chem. 2016;16(12):980-95.
Other Publications
- Roy S, Haloi P, Siva Lokesh B, Chawla S, Konkimalla VB, Jaiswal A. Biocompatible quaternary pullulan functionalized 2D MoS2 glycosheet-based non-leaching and infection-resistant coatings for indwelling medical implants. Journal of Materials Chemistry B. 2023; 202311, 10418 - 10432.
- Singh P, Haloi P, Singh K, Roy S, Sarkar A, Siva Lokesh B, Choudhary R, Mohite C, Chawla S, Konkimalla VB, Sanpui P, Jaiswal A. Palladium Nanocapsules for Photothermal Therapy in the NIR-II Biological Window. ACS Applied Materials & Interfaces. 2023. 15(33), 39081-39098.
- Roy S, Haloi P, Choudhary R, Chawla S, Kumari M, Konkimalla VB, Jaiswal A. Quaternary Pullulan functionalized 2D MoS2 glycosheets: A potent bactericidal nanoplatform for efficient wound disinfection and healing. ACS Applied Materials & Interfaces. 2023; 15(20), 24209–24227.
- Roy S, Kumari M, Haloi P, Chawla S, Konkimalla VB, Kumar A, Kashyap HK and Jaiswal A. Quaternary Ammonium Substituted Pullulan Accelerates Wound Healing and Disinfects Staphylococcus aureus Infected Wounds in Mouse Through an Atypical ‘Non-Pore Forming’ Pathway of Bacterial Membrane Disruption. Biomaterials Science. 2022; 10: 581-601.
- Malwal SR, Dharmarajan S, Perumal Y, Konkimalla VB and Chakrapani H. Design, Synthesis and Evaluation of Thiol-Activated Sources of Sulfur Dioxide (SO2) as Antimycobacterial Agents. Journal of Medicinal Chemistry. 2012; 55(1):553-7.
- Polier G, Ding J, Konkimalla VB, Eick D, Ribeiro N, Köhler R, Giaisi M, Efferth T, Desaubry L, Krammer PH, Li-Weber M. Wogonin and related natural flavones are inhibitors of CDK9 that induce apoptosis in cancer cells by transcriptional suppression of Mcl-1. Cell Death and Disease. 2011; 2(7):e182.
- Youns M, Fu YJ, Zu YG, Kramer A, Konkimalla VB, Radlwimmer B, Sültmann H, Efferth T. Sensitivity and resistance towards isoliquiritigenin, doxorubicin, and methotrexate in T cell acute lymphoblastic leukemia cell lines by pharmacogenomics. Naunyn Schmiedebergs Archives in Pharmacology. 2010; 382(3):221-34.
- Konkimalla VB, Blunder M, Korn B, Soomro SA, Jansen H, Chang W, Posner GH, Bauer R and Efferth T. Effect of artemisinins and other endoperoxides on nitric oxide-related signaling pathway in RAW 264.7 mouse macrophage cells. Nitric Oxide. 2008; 19:184-191.
- Efferth T, Konkimalla VB, Wang YF, Sauerbrey A, Meinhardt S, Zintl F, Mattern J and Volm M. Prediction of Broad Spectrum Resistance of Tumors towards Anticancer Drugs`. Clinical Cancer Research. 2008; 14(8):2405-2412.
- Kelter G, Steinbach D, Konkimalla VB, Tahara T, Taketani S, Fiebig HH and Efferth T. Role of transferrin receptor and the ABC transporters ABCB6 and ABCB7 for resistance and differentiation of tumor cells towards artesunate. PLoS ONE. 2007; 2(8): e798.
- Konkimalla VB and Chandra N. Determinants of histamine recognition: implications for the design of antihistamines. Biochemical and Biophysical Research Communications. 2003; 309(2):425-31.
Review articles
- Gaikwad M, Konkimalla VB and Salunke-Gawali S. Metal complexes as topoisomerase inhibitors. Inorganica Chimica Acta. 2022; 542: 121089.
- Pal S and Konkimalla VB. Hormetic potential of Sulforaphane (SFN) in switching cells' fate towards survival or death. Mini Rev Med Chem. 2016; 16(12): 980-995.
- Satpathy R, Konkimalla VB, Ratha J. Application of bioinformatics tools and databases in microbial dehalogenation research: A review. Applied Biochemistry and Microbiology. 2015; 51(1):11-20.
- Dash TK and Konkimalla VB. Nanoformulations for Delivery of Biomolecules; Focus on Liposomal Variants for siRNA Delivery. Critical reviews in therapeutic drug delivery system. 2013; 30(6):469-493.
- Dash TK and Konkimalla VB. Polymeric modifications and its implication in drug delivery: Poly-ε-caprolactone (PCL) as a model polymer. Molecular Pharmaceutics. 2012; 9(9):2365-79.
- Dash TK and Konkimalla VB. Poly-ε-caprolactone based formulations for drug delivery and tissue engineering: a review. Journal of Controlled Release. 2011; 21; 158(1): 15-33.
- Konkimalla VB and Efferth T. Evidence-Based Chinese Medicine for Cancer Therapy. Journal of Ethnopharmacology. 2008; 116(2):207-210.
- Efferth T, Li PC, Konkimalla VB and Kaina B. From traditional Chinese medicine to rational cancer therapy. Trends in Molecular Medicine. 2007; 13(8):353-361.
- Efferth T, Fu YJ, Zu YG, Schwarz G, Konkimalla VB, and Wink M. Molecular target-guided tumor therapy with natural products derived from traditional Chinese medicine. Current Medicinal Chemistry. 2007; 14(19):2024-2032.
- Konkimalla VB, Suhas VL, Chandra NR, Gebhart E and Efferth T. Diagnosis and therapy of oral squamous cell carcinoma. Expert Reviews in Anticancer Therapy. 2007; 7(3):317-329.
Book Chapters
- Siva Lokesh B and Konkimalla VB. Novel Strategies for Targeted Nanotherapeutics for cancer control. In: Novel molecular oncotargets and Nano-oncotherapeutics. Cambridge Scholar Publishing. 2022. Accepted.
- Ajmeera S and Konkimalla VB. Nanoformulations to Limit Challenges of Conventional Therapy against Hepatocellular Carcinoma – An Overview. In: Nanotherapeutics for the Treatment of Hepatocellular Carcinoma. Bentham Science Publishers. 2022, pp 166-218.
- Dash TK and Konkimalla VB. Modification of Cyclodextrin for Improvement of Complexation and Formulation Properties. In: Wiley-Scriverner. In: Handbook of Polymers for Pharmaceutical Technologies: Biodegradable Polymers. Vol 3. 2015, pp 205-224. ISBN: 978-1-119-04142-9.
- Konkimalla VB. Predicting Cross-Reactivity from Computational Studies for Pre-evaluation of Specific Hepatic Glycogen Phosphorylase Inhibitors. In: Springer. Bioinformatics and Biomedical Engineering. In: Lecture Notes in Computer Science. 2015, 9044, pp 674-682.
- Konkimalla VB, Kramer A, Fu Y and Efferth T. Identification of Molecular Determinants for Cytotoxicity of Isoloquiritigenin from Liquorice (Glycyrrhiza glabra) towards Leukemia Cell Lines. In: Wiley-VCH. Deutsche Forschungsgemeinschaft (DFG) (Ed.), G. Eisenbrand (Ed.). In: Risk Assessment of Phytochemicals in Food: Novel Approaches. 2010, pp 429. ISBN: 978-3-527-32929-8.
- Konkimalla VB and Efferth T. Molecular mechanisms and interactions responsible for radio- and chemoresistance of tumors and their modulation by natural products from Ayurveda. In: R. Arora (Ed.) Herbal Medicine. A cancer chemopreventive and therapeutic perspective. 2010, 7(33). 511-530.